105 results on '"Lipids"'
Search Results
2. JAK/STAT Inhibition Normalizes Lipid Composition in 3D Human Epidermal Equivalents Challenged with Th2 Cytokines.
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Flori, Enrica, Cavallo, Alessia, Mosca, Sarah, Kovacs, Daniela, Cota, Carlo, Zaccarini, Marco, Di Nardo, Anna, Bottillo, Grazia, Maiellaro, Miriam, Camera, Emanuela, and Cardinali, Giorgia
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METABOLIC regulation , *CYTOKINES , *LIPID metabolism , *LIPIDS , *FILAGGRIN , *CARBONIC anhydrase - Abstract
Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism. [ABSTRACT FROM AUTHOR]
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- 2024
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3. 4-Oxo-2-Nonenal- and Agitation-Induced Aggregates of α-Synuclein and Phosphorylated α-Synuclein with Distinct Biophysical Properties and Biomedical Applications.
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Wang, Tie, Liu, Weijin, Zhang, Qidi, Jiao, Jie, Wang, Zihao, Gao, Ge, and Yang, Hui
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ALPHA-synuclein , *ENZYME-linked immunosorbent assay , *PARKINSON'S disease , *LIPIDS , *TRANSMISSION electron microscopy , *TRANSGENIC mice - Abstract
α-Synuclein (α-syn) can form oligomers, protofibrils, and fibrils, which are associated with the pathogenesis of Parkinson's disease and other synucleinopathies. Both the lipid peroxidation product 4-oxo-2-nonenal (ONE) and agitation can induce aggregation of α-syn and phosphorylated α-syn. Thus, clarification of the characteristics of different α-syn species could help to select suitable aggregates for diagnosis and elucidate the pathogenesis of diseases. Here, we characterized ONE-induced wild-type (WT) α-syn aggregates (OW), ONE-induced phosphorylated α-syn (p-α-syn) aggregates (OP), agitation-induced α-syn preformed fibrils (PFF), and agitation-induced p-α-syn preformed fibrils (pPFF). Thioflavin T (ThT) dying demonstrated that OW and OP had fewer fibrils than the PFF and pPFF. Transmission electron microscopy revealed that the lengths of PFF and pPFF were similar, but the diameters differed. OW and OP had more compact structures than PFF and pPFF. Aggregation of p-α-syn was significantly faster than WT α-syn. Furthermore, OW and OP were more sodium dodecyl sulfate-stable and proteinase K-resistant, suggesting greater stability and compactness, while aggregates of PFF and pPFF were more sensitive to proteinase K treatment. Both ONE- and agitation-induced aggregates were cytotoxic when added exogenously to SH-SY5Y cells with increasing incubation times, but the agitation-induced aggregates caused cell toxicity in a shorter time and more p-α-syn inclusions. Similarly, p-proteins were more cytotoxic than non-p-proteins. Finally, all four aggregates were used as standard antigens to establish sandwich enzyme-linked immunosorbent assay (ELISA). The results showed that the recognition efficiency of OW and OP was more sensitive than that of PFF and pPFF. The OW- and OP-specific ELISA for detection of p-α-syn and α-syn in plasma samples of Thy1-α-syn transgenic mice showed that the content of aggregates could reflect the extent of disease. ONE and agitation induced the formation of α-syn aggregates with distinct biophysical properties and biomedical applications. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Nuclear Phospholipids and Signaling: An Update of the Story.
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Casalin, Irene, Ceneri, Eleonora, Ratti, Stefano, Manzoli, Lucia, Cocco, Lucio, and Follo, Matilde Y.
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CELL communication , *INOSITOL , *PHOSPHOINOSITIDES , *PHOSPHOLIPIDS , *LIPIDS - Abstract
In the last three decades, the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A considerable amount of interest has been raised about nuclear inositol lipids, mainly because of their role in signaling acting. Here, we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling, both in physiological and pathological conditions. [ABSTRACT FROM AUTHOR]
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- 2024
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5. The Role of Fatty Acid Synthase in the Vascular Smooth Muscle Cell to Foam Cell Transition.
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Bogan, Bethany J., Williams, Holly C., Holden, Claire M., Patel, Vraj, Joseph, Giji, Fierro, Christopher, Sepulveda, Hugo, Taylor, W. Robert, Rezvan, Amir, and San Martin, Alejandra
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FATTY acid synthases , *FOAM cells , *VASCULAR smooth muscle , *MUSCLE cells , *FREE fatty acids , *LIPIDS - Abstract
Vascular smooth muscle cells (VSMCs), in their contractile and differentiated state, are fundamental for maintaining vascular function. Upon exposure to cholesterol (CHO), VSMCs undergo dedifferentiation, adopting characteristics of foam cells—lipid-laden, macrophage-like cells pivotal in atherosclerotic plaque formation. CHO uptake by VSMCs leads to two primary pathways: ABCA1-mediated efflux or storage in lipid droplets as cholesterol esters (CEs). CE formation, involving the condensation of free CHO and fatty acids, is catalyzed by sterol O-acyltransferase 1 (SOAT1). The necessary fatty acids are synthesized by the lipogenic enzyme fatty acid synthase (FASN), which we found to be upregulated in atherosclerotic human coronary arteries. This observation led us to hypothesize that FASN-mediated fatty acid biosynthesis is crucial in the transformation of VSMCs into foam cells. Our study reveals that CHO treatment upregulates FASN in human aortic SMCs, concurrent with increased expression of CD68 and upregulation of KLF4, markers associated with the foam cell transition. Crucially, downregulation of FASN inhibits the CHO-induced upregulation of CD68 and KLF4 in VSMCs. Additionally, FASN-deficient VSMCs exhibit hindered lipid accumulation and an impaired transition to the foam cell phenotype following CHO exposure, while the addition of the fatty acid palmitate, the main FASN product, exacerbates this transition. FASN-deficient cells also show decreased SOAT1 expression and elevated ABCA1. Notably, similar effects are observed in KLF4-deficient cells. Our findings demonstrate that FASN plays an essential role in the CHO-induced upregulation of KLF4 and the VSMC to foam cell transition and suggest that targeting FASN could be a novel therapeutic strategy to regulate VSMC phenotypic modulation. [ABSTRACT FROM AUTHOR]
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- 2024
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6. In Vitro Lipid Overload Affects Cellular Proliferation, Apoptosis, and Senescence in a Time-Dependent Manner in HepG2 Hepatocytes and LX-2 Hepatic Stellate Cells.
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Campos-Espinosa, Adriana, Guzmán, Carolina, Medina-Ávila, Karla Zaira, and Gutierrez-Reyes, Gabriela
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LIVER cells , *CELL proliferation , *LIVER regeneration , *APOPTOSIS , *OLEIC acid , *CELLULAR aging , *LIPIDS - Abstract
Different cellular mechanisms influence steatotic liver disease (SLD) progression. The influence of different levels of steatogenic inputs has not been studied in hepatocytes and hepatic stellate cells (HSCs). Methods: HepG2 hepatocytes and LX-2 HSCs were cultured in mild (MS) and severe (SS) steatogenic conditions. TGF-β stimulation was also tested for HSCs in control (T) and steatogenic conditions (MS-T and SS-T). Steatosis was stained with Oil Red, and the proliferation was assayed via WST-8 reduction, apoptosis via flow cytometry, and senescence via SA-β-galactosidase activity. Results: Regarding hepatocytes, steatosis progressively increased; proliferation was lower in MS and SS; and the viability of both conditions significantly decreased at 72 h. Apoptosis increased in MS at 72 h, while it decreased in SS. Senescence increased in MS and diminished in SS. Regarding HSCs, the SS and SS-T groups showed no proliferation, and the viability was reduced in MS at 72 h and in SS and SS-T. The LX-2 cells showed increased apoptosis in SS and SS-T at 24 h, and in MS and MS-T at 72 h. Senescence decreased in MS, SS, and SS-T. Conclusions: Lipid overload induces differential effects depending on the cell type, the steatogenic input level, and the exposure time. Hepatocytes are resilient to mild steatosis but susceptible to high lipotoxicity. HSCs are sensitive to lipid overload, undergoing apoptosis and lowering senescence and proliferation. Collectively, these data may help explain the development of steatosis and fibrosis in SLD. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Cytokines and Epidermal Lipid Abnormalities in Atopic Dermatitis: A Systematic Review.
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Upadhyay, Parth R., Seminario-Vidal, Lucia, Abe, Brian, Ghobadi, Cyrus, and Sims, Jonathan T.
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ATOPIC dermatitis , *FILAGGRIN , *CYTOKINES , *LIPIDS , *HUMAN abnormalities , *SKIN diseases - Abstract
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant TH2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with TH1 and TH17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Blood-Derived Lipid and Metabolite Biomarkers in Cardiovascular Research from Clinical Studies: A Recent Update.
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Kale, Dipali, Fatangare, Amol, Phapale, Prasad, and Sickmann, Albert
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LIPIDOMICS , *BLOOD lipids , *NUCLEAR magnetic resonance , *MEDICAL research , *BIOMARKERS , *LIPIDS - Abstract
The primary prevention, early detection, and treatment of cardiovascular disease (CVD) have been long-standing scientific research goals worldwide. In the past decades, traditional blood lipid profiles have been routinely used in clinical practice to estimate the risk of CVDs such as atherosclerotic cardiovascular disease (ASCVD) and as treatment targets for the primary prevention of adverse cardiac events. These blood lipid panel tests often fail to fully predict all CVD risks and thus need to be improved. A comprehensive analysis of molecular species of lipids and metabolites (defined as lipidomics and metabolomics, respectively) can provide molecular insights into the pathophysiology of the disease and could serve as diagnostic and prognostic indicators of disease. Mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analysis have been increasingly used to study the metabolic changes that occur during CVD pathogenesis. In this review, we provide an overview of various MS-based platforms and approaches that are commonly used in lipidomics and metabolomics workflows. This review summarizes the lipids and metabolites in human plasma/serum that have recently (from 2018 to December 2022) been identified as promising CVD biomarkers. In addition, this review describes the potential pathophysiological mechanisms associated with candidate CVD biomarkers. Future studies focused on these potential biomarkers and pathways will provide mechanistic clues of CVD pathogenesis and thus help with the risk assessment, diagnosis, and treatment of CVD. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Loss of Lipid Carrier ApoE Exacerbates Brain Glial and Inflammatory Responses after Lysosomal GBA1 Inhibition.
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Connolly, Kyle J., Margaria, Juliette, Di Biase, Erika, Cooper, Oliver, Hallett, Penelope J., and Isacson, Ole
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LEWY body dementia , *APOLIPOPROTEIN E , *GLYCOLIPIDS , *COMPLEMENT (Immunology) , *INFLAMMATION , *LIPIDS - Abstract
Tightly regulated and highly adaptive lipid metabolic and transport pathways are critical to maintaining brain cellular lipid homeostasis and responding to lipid and inflammatory stress to preserve brain function and health. Deficits in the lipid handling genes APOE and GBA1 are the most significant genetic risk factors for Lewy body dementia and related dementia syndromes. Parkinson's disease patients who carry both APOE4 and GBA1 variants have accelerated cognitive decline compared to single variant carriers. To investigate functional interactions between brain ApoE and GBA1, in vivo GBA1 inhibition was tested in WT versus ApoE-deficient mice. The experiments demonstrated glycolipid stress caused by GBA1 inhibition in WT mice induced ApoE expression in several brain regions associated with movement and dementia disorders. The absence of ApoE in ApoE-KO mice amplified complement C1q elevations, reactive microgliosis and astrocytosis after glycolipid stress. Mechanistically, GBA1 inhibition triggered increases in cell surface and intracellular lipid transporters ABCA1 and NPC1, respectively. Interestingly, the absence of NPC1 in mice also triggered elevations of brain ApoE levels. These new data show that brain ApoE, GBA1 and NPC1 functions are interconnected in vivo, and that the removal or reduction of ApoE would likely be detrimental to brain function. These results provide important insights into brain ApoE adaptive responses to increased lipid loads. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Crystal Structure of the ORP8 Lipid Transport ORD Domain: Model of Lipid Transport.
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Eisenreichova, Andrea, Klima, Martin, Anila, Midhun Mohan, Koukalova, Alena, Humpolickova, Jana, Różycki, Bartosz, and Boura, Evzen
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CRYSTAL structure , *INTRACELLULAR membranes , *LIPIDS , *CELL membranes , *HYDROPHOBIC interactions , *HYDROXYCHOLESTEROLS - Abstract
ORPs are lipid-transport proteins belonging to the oxysterol-binding protein family. They facilitate the transfer of lipids between different intracellular membranes, such as the ER and plasma membrane. We have solved the crystal structure of the ORP8 lipid transport domain (ORD8). The ORD8 exhibited a β-barrel fold composed of anti-parallel β-strands, with three α-helices replacing β-strands on one side. This mixed alpha–beta structure was consistent with previously solved structures of ORP2 and ORP3. A large cavity (≈1860 Å3) within the barrel was identified as the lipid-binding site. Although we were not able to obtain a lipid-bound structure, we used computer simulations based on our crystal structure to dock PS and PI4P molecules into the putative lipid-binding site of the ORD8. Comparative experiments between the short ORD8ΔLid (used for crystallography) and the full-length ORD8 (lid containing) revealed the lid's importance for stable lipid binding. Fluorescence assays revealed different transport efficiencies for PS and PI4P, with the lid slowing down transport and stabilizing cargo. Coarse-grained simulations highlighted surface-exposed regions and hydrophobic interactions facilitating lipid bilayer insertion. These findings enhance our comprehension of ORD8, its structure, and lipid transport mechanisms, as well as provide a structural basis for the design of potential inhibitors. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Functional Characterization of Lysophospholipids by Proteomic and Lipidomic Analysis of Fibroblast-like Synoviocytes.
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Timm, Thomas, Hild, Christiane, Liebisch, Gerhard, Rickert, Markus, Lochnit, Guenter, and Steinmeyer, Juergen
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LIQUID scintillation counting , *PROTEOMICS , *KNEE joint , *LYSOPHOSPHOLIPIDS , *JOINTS (Anatomy) , *PHOSPHOLIPIDS , *SCINTILLATORS - Abstract
Synovial fluid (SF) from human knee joints with osteoarthritis (OA) has elevated levels of lysophosphatidylcholine (LPC) species, but their functional role is not well understood. This in vitro study was designed to test the hypothesis that various LPCs found elevated in OA SF and their metabolites, lysophosphatidic acids (LPAs), modulate the abundance of proteins and phospholipids (PLs) in human fibroblast-like synoviocytes (FLSs), with even minute chemical variations in lysophospholipids determining the extent of regulation. Cultured FLSs (n = 5–7) were treated with one of the LPC species, LPA species, IL-1β, or a vehicle. Tandem mass tag peptide labeling coupled with LC-MS/MS/MS was performed to quantify proteins. The expression of mRNA from regulated proteins was analyzed using RT-PCR. PL synthesis was determined via ESI-MS/MS, and the release of radiolabeled PLs was determined by means of liquid scintillation counting. In total, 3960 proteins were quantified using multiplexed MS, of which 119, 8, and 3 were significantly and reproducibly regulated by IL-1β, LPC 16:0, and LPC 18:0, respectively. LPC 16:0 significantly inhibited the release of PLs and the synthesis of phosphatidylcholine, LPC, and sphingomyelin. Neither LPC metabolite—LPA 16:0 nor LPA 18:0—had any reproducible effect on the levels of each protein. In conclusion, small chemical variations in LPC species can result in the significantly altered expression and secretion of proteins and PLs from FLSs. IL-1β influenced all proteins that were reproducibly regulated by LPC 16:0. LPC species are likely to modulate FLS protein expression only in more advanced OA stages with low IL-1β levels. None of the eight proteins being significantly regulated by LPC 16:0 have been previously reported in OA. However, our in vitro findings show that the CD81 antigen, calumenin, and B4E2C1 are promising candidates for further study, focusing in particular on their potential ability to modulate inflammatory and catabolic mechanisms. [ABSTRACT FROM AUTHOR]
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- 2023
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12. TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury.
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Shafit-Zagardo, Bridget, Sidoli, Simone, Goldman, James E., DuBois, Juwen C., Corboy, John R., Strittmatter, Stephen M., Guzik, Hillary, Edema, Ukuemi, Arackal, Anita G., Botbol, Yair M., Merheb, Emilio, Nagra, Rashed M., and Graff, Sarah
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MYELIN oligodendrocyte glycoprotein , *MULTIPLE sclerosis , *CENTRAL nervous system injuries , *ALZHEIMER'S disease , *MYELIN proteins , *DEMYELINATION , *MEMBRANE proteins - Abstract
During inflammatory, demyelinating diseases such as multiple sclerosis (MS), inflammation and axonal damage are prevalent early in the course. Axonal damage includes swelling, defects in transport, and failure to clear damaged intracellular proteins, all of which affect recovery and compromise neuronal integrity. The clearance of damaged cell components is important to maintain normal turnover and restore homeostasis. In this study, we used mass spectrometry to identify insoluble proteins within high-speed/mercaptoethanol/sarcosyl-insoluble pellets from purified white matter plaques isolated from the brains of individuals with relapsing–remitting MS (RRMS). We determined that the transmembrane protein 106B (TMEM106B), normally lysosome-associated, is insoluble in RRMS plaques relative to normal-appearing white matter from individuals with Alzheimer's disease and non-neurologic controls. Relative to wild-type mice, hypomorphic mice with a reduction in TMEM106B have increased axonal damage and lipid droplet accumulation in the spinal cord following myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis. Additionally, the corpora callosa from cuprizone-challenged hypomorphic mice fail to clear lipid droplets efficiently during remyelination, suggesting that when TMEM106B is compromised, protein and lipid clearance by the lysosome is delayed. As TMEM106B contains putative lipid- and LC3-binding sites, further exploration of these sites is warranted. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Molecular Mechanisms of Lipid-Based Metabolic Adaptation Strategies in Response to Cold.
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Wu, Gang, Baumeister, Ralf, and Heimbucher, Thomas
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COLD adaptation , *NUCLEAR receptors (Biochemistry) , *WARM-blooded animals , *PEROXISOME proliferator-activated receptors , *HEMORRHAGIC shock , *LIPIDS , *LIPID metabolism - Abstract
Temperature changes and periods of detrimental cold occur frequently for many organisms in their natural habitats. Homeothermic animals have evolved metabolic adaptation strategies to increase mitochondrial-based energy expenditure and heat production, largely relying on fat as a fuel source. Alternatively, certain species are able to repress their metabolism during cold periods and enter a state of decreased physiological activity known as torpor. By contrast, poikilotherms, which are unable to maintain their internal temperature, predominantly increase membrane fluidity to diminish cold-related damage from low-temperature stress. However, alterations of molecular pathways and the regulation of lipid-metabolic reprogramming during cold exposure are poorly understood. Here, we review organismal responses that adjust fat metabolism during detrimental cold stress. Cold-related changes in membranes are detected by membrane-bound sensors, which signal to downstream transcriptional effectors, including nuclear hormone receptors of the PPAR (peroxisome proliferator-activated receptor) subfamily. PPARs control lipid metabolic processes, such as fatty acid desaturation, lipid catabolism and mitochondrial-based thermogenesis. Elucidating the underlying molecular mechanisms of cold adaptation may improve beneficial therapeutic cold treatments and could have important implications for medical applications of hypothermia in humans. This includes treatment strategies for hemorrhagic shock, stroke, obesity and cancer. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Endothelial Function in Dyslipidemia: Roles of LDL-Cholesterol, HDL-Cholesterol and Triglycerides.
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Higashi, Yukihito
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HDL cholesterol , *LDL cholesterol , *DYSLIPIDEMIA , *TRIGLYCERIDES , *ENDOTHELIUM diseases , *CARDIOVASCULAR diseases , *LIPIDS - Abstract
Dyslipidemia is associated with endothelial dysfunction. Endothelial dysfunction is the initial step for atherosclerosis, resulting in cardiovascular complications. It is clinically important to break the process of endothelial dysfunction to cardiovascular complications in patients with dyslipidemia. Lipid-lowering therapy enables the improvement of endothelial function in patients with dyslipidemia. It is likely that the relationships of components of a lipid profile such as low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides with endothelial function are not simple. In this review, we focus on the roles of components of a lipid profile in endothelial function. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Changes in Liver Lipidomic Profile in G2019S- LRRK2 Mouse Model of Parkinson's Disease.
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Corral Nieto, Yaiza, Yakhine-Diop, Sokhna M. S., Moreno-Cruz, Paula, Manrique García, Laura, Gabrielly Pereira, Amanda, Morales-García, José A., Niso-Santano, Mireia, González-Polo, Rosa A., Uribe-Carretero, Elisabet, Durand, Sylvère, Maiuri, Maria Chiara, Paredes-Barquero, Marta, Alegre-Cortés, Eva, Canales-Cortés, Saray, López de Munain, Adolfo, Pérez-Tur, Jordi, Pérez-Castillo, Ana, Kroemer, Guido, Fuentes, José M., and Bravo-San Pedro, José M.
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PARKINSON'S disease , *DARDARIN , *LABORATORY mice , *ANIMAL disease models , *CARBOHYDRATE metabolism - Abstract
The identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis. To achieve this goal, we used mass spectrometry technology to determine the complete metabolomic profile of liver and striatal tissue samples from WT mice, 6-hydroxydopamine-treated mice (idiopathic model) and mice affected by the G2019S-LRRK2 mutation in LRRK2/PARK8 gene (genetic model). This analysis revealed that the metabolism of carbohydrates, nucleotides and nucleosides was similarly altered in the liver from the two PD mouse models. However, long-chain fatty acids, phosphatidylcholine and other related lipid metabolites were only altered in hepatocytes from G2019S-LRRK2 mice. In summary, these results reveal specific differences, mainly in lipid metabolism, between idiopathic and genetic PD models in peripheral tissues and open up new possibilities to better understand the etiology of this neurological disorder. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Diallyl Trisulfide, a Biologically Active Component of Garlic Essential Oil, Decreases Male Fertility in Sitotroga cerealella by Impairing Dimorphic Spermatogenesis, Sperm Motility and Lipid Homeostasis.
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Shah, Sakhawat, Elgizawy, Karam Khamis, Shi, Chun-Mei, Yao, Hucheng, Yan, Wen-Han, Li, Yu, Wang, Xiao-Ping, Wu, Gang, and Yang, Feng-Lian
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SPERM motility , *FERTILITY , *SPERMATOGENESIS , *GARLIC , *SPREADING cortical depression , *HOMEOSTASIS , *LIPIDS , *ESSENTIAL oils , *INHIBIN - Abstract
Diallyl trisulfide (DAT) is a biologically active component of garlic essential oil and exhibits multi-targeted activity against many organisms. The current study tested the capacity of DAT to decrease the male fertility of Sitotroga cerealella. The effects on testis morphology, sperm number, motility, and lipid homeostasis were observed in adult males fumigated with DAT at a dose of 0.01 μL/L in air. The results indicated that the DAT significantly decreased the dimorphic sperm number. Meanwhile, the ultrastructural analysis of the sperm showed that the DAT caused malformed and aberrant structures of mitochondrial derivatives of dimorphic sperm. Additionally, the lipid homeostasis and ATP contents in the male adults were significantly decreased after treatment. Moreover, the total sperm motility was reduced, while the wave-propagation velocity, amplitude, frequency, and wavelength were significantly decreased compared with the controls. Overall, this study reported, for the first time, that DAT impairs energy metabolism, inhibits dimorphic spermatogenesis, and decreases sperm motility, while these abnormalities in sperm lead to adult-male infertility. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Lipids of Platelet-Rich Fibrin Reduce the Inflammatory Response in Mesenchymal Cells and Macrophages.
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Kargarpour, Zahra, Panahipour, Layla, Mildner, Michael, Miron, Richard J., and Gruber, Reinhard
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PLATELET-rich fibrin , *MESENCHYMAL stem cells , *LIPIDS , *INFLAMMATION , *BLOOD lipids , *MACROPHAGES - Abstract
Platelet-rich fibrin (PRF) has a potent anti-inflammatory activity but the components mediating this effect remain unknown. Blood lipids have anti-inflammatory properties. The question arises whether this is also true for the lipid fraction of PRF. To answer this question, lipid fractions of solid and liquid PRF were tested for their potential to lower the inflammatory response of ST2 bone marrow stromal cells and primary bone marrow macrophages exposed to IL1β and TNFα, and LPS, respectively. Cytokine production and the underlying signalling pathway were analysed by RT-PCR, immunoassays, and Western blotting. We report here that lipids from solid and liquid PRF substantially lowered cytokine-induced expression of IL6, CCL2 and CCL5 in ST2 cells. Moreover, the inflammatory response induced by Pam3CSK4, the agonist of Toll-like receptor (TLR) TLR2, was partially reduced by the lipid extracts in ST2 cells. The PRF lipids further reduced the LPS-induced expression of IL1β, IL6 and CCL5 in macrophages at the transcriptional level. This was confirmed by showing the ability of PRF lipids to diminish IL6 at the protein level in ST2 cells and macrophages. Likewise, PRF lipid extracts reduced the phosphorylation of p38 and JNK and moderately decreased the phosphorylation of NFκB-p65 in ST2 cells. These findings suggest that the lipid fraction is at least partially responsible for the anti-inflammatory activity of PRF in vitro. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Erythrocyte Plasma Membrane Lipid Composition Mirrors That of Neurons and Glial Cells in Murine Experimental In Vitro and In Vivo Inflammation.
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Stanzani, Agnese, Sansone, Anna, Brenna, Cinzia, Baldassarro, Vito Antonio, Alastra, Giuseppe, Lorenzini, Luca, Chatgilialoglu, Chryssostomos, Laface, Ilaria, Ferreri, Carla, Neri, Luca Maria, and Calzà, Laura
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BLOOD lipids , *ERYTHROCYTE membranes , *NEUROGLIA , *CELL membranes , *MIRROR neurons , *MEMBRANE lipids , *MONOUNSATURATED fatty acids , *MYELIN proteins - Abstract
Lipid membrane turnover and myelin repair play a central role in diseases and lesions of the central nervous system (CNS). The aim of the present study was to analyze lipid composition changes due to inflammatory conditions. We measured the fatty acid (FA) composition in erythrocytes (RBCs) and spinal cord tissue (gas chromatography) derived from mice affected by experimental allergic encephalomyelitis (EAE) in acute and remission phases; cholesterol membrane content (Filipin) and GM1 membrane assembly (CT-B) in EAE mouse RBCs, and in cultured neurons, oligodendroglial cells and macrophages exposed to inflammatory challenges. During the EAE acute phase, the RBC membrane showed a reduction in polyunsaturated FAs (PUFAs) and an increase in saturated FAs (SFAs) and the omega-6/omega-3 ratios, followed by a restoration to control levels in the remission phase in parallel with an increase in monounsaturated fatty acid residues. A decrease in PUFAs was also shown in the spinal cord. CT-B staining decreased and Filipin staining increased in RBCs during acute EAE, as well as in cultured macrophages, neurons and oligodendrocyte precursor cells exposed to inflammatory challenges. This regulation in lipid content suggests an increased cell membrane rigidity during the inflammatory phase of EAE and supports the investigation of peripheral cell membrane lipids as possible biomarkers for CNS lipid membrane concentration and assembly. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Cellular and Molecular Control of Lipid Metabolism in Idiopathic Pulmonary Fibrosis: Clinical Application of the Lysophosphatidic Acid Pathway.
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Nakamura, Yusuke and Shimizu, Yasuo
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IDIOPATHIC pulmonary fibrosis , *LIPID metabolism , *LYSOPHOSPHOLIPIDS , *METABOLIC regulation , *VASCULAR endothelial cells , *LIPIDS - Abstract
Idiopathic pulmonary fibrosis (IPF) is a representative disease that causes fibrosis of the lungs. Its pathogenesis is thought to be characterized by sustained injury to alveolar epithelial cells and the resultant abnormal tissue repair, but it has not been fully elucidated. IPF is currently difficult to cure and is known to follow a chronic progressive course, with the patient's survival period estimated at about three years. The disease occasionally exacerbates acutely, leading to a fatal outcome. In recent years, it has become evident that lipid metabolism is involved in the fibrosis of lungs, and various reports have been made at the cellular level as well as at the organic level. The balance among eicosanoids, sphingolipids, and lipid composition has been reported to be involved in fibrosis, with particularly close attention being paid to a bioactive lipid "lysophosphatidic acid (LPA)" and its pathway. LPA signals are found in a wide variety of cells, including alveolar epithelial cells, vascular endothelial cells, and fibroblasts, and have been reported to intensify pulmonary fibrosis via LPA receptors. For instance, in alveolar epithelial cells, LPA signals reportedly induce mitochondrial dysfunction, leading to epithelial damage, or induce the transcription of profibrotic cytokines. Based on these mechanisms, LPA receptor inhibitors and the metabolic enzymes involved in LPA formation are now considered targets for developing novel means of IPF treatment. Advances in basic research on the relationships between fibrosis and lipid metabolism are opening the path to new therapies targeting lipid metabolism in the treatment of IPF. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Lipid ROS- and Iron-Dependent Ferroptotic Cell Death in Unicellular Algae Chlamydomonas reinhardtii.
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Srinivasan, Ramachandran, Han, Hyo-Shim, Subramanian, Parthiban, Mageswari, Anbazhagan, Kim, Seong-Hoon, Tirumani, Srikanth, Maurya, Vaibhav Kumar, Muthukaliannan, Gothandam Kodiveri, and Ramya, Mohandass
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CELL death , *HEAT shock proteins , *CHLAMYDOMONAS reinhardtii , *SHOCK therapy , *REACTIVE oxygen species , *LIPIDS , *IRON - Abstract
The phenomenon of heat stress leading to ferroptosis-like cell death has recently been observed in bacteria as well as plant cells. Despite recent findings, the evidence of ferroptosis, an iron-dependent cell death remains unknown in microalgae. The present study aimed to investigate if heat shock could induce reactive oxygen species (ROS) and iron-dependent ferroptotic cell death in Chlamydomonas reinhardtii in comparison with RSL3-induced ferroptosis. After RSL3 and heat shock (50 °C) treatments with or without inhibitors, Chlamydomonas cells were evaluated for cell viability and the induction of ferroptotic biomarkers. Both the heat shock and RSL3 treatment were found to trigger ferroptotic cell death, with hallmarks of glutathione–ascorbic acid depletion, GPX5 downregulation, mitochondrial dysfunction, an increase in cytosolic calcium, ROS production, lipid peroxidation, and intracellular iron accumulation via heme oxygenase-1 activation (HO-1). Interestingly, the cells preincubated with ferroptosis inhibitors (ferrostatin-1 and ciclopirox) significantly reduced RSL3- and heat-induced cell death by preventing the accumulation of Fe2+ and lipid ROS. These findings reveal that ferroptotic cell death affects the iron homeostasis and lipid peroxidation metabolism of Chlamydomonas, indicating that cell death pathways are evolutionarily conserved among eukaryotes. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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21. Grapevine-Associated Lipid Signalling Is Specifically Activated in an Rpv3 Background in Response to an Aggressive P. viticola Pathovar.
- Author
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Laureano, Gonçalo, Santos, Catarina, Gouveia, Catarina, Matos, Ana Rita, and Figueiredo, Andreia
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DOWNY mildew diseases , *GENE families , *LIPIDS , *LIPID metabolism , *FATTY acids , *VITIS vinifera , *GENE expression , *PHOSPHOLIPASES - Abstract
Vitis vinifera L. is highly susceptible to the biotrophic pathogen Plasmopara viticola. To control the downy mildew disease, several phytochemicals are applied every season. Recent European Union requirements to reduce the use of chemicals in viticulture have made it crucial to use alternative and more sustainable approaches to control this disease. Our previous studies pinpoint the role of fatty acids and lipid signalling in the establishment of an incompatible interaction between grapevine and P. viticola. To further understand the mechanisms behind lipid involvement in an effective defence response we have analysed the expression of several genes related to lipid metabolism in three grapevine genotypes: Chardonnay (susceptible); Regent (tolerant), harbouring an Rpv3-1 resistance loci; and Sauvignac (resistant) that harbours a pyramid of Rpv12 and Rpv3-1 resistance loci. A highly aggressive P. viticola isolate was used (NW-10/16). Moreover, we have characterised the grapevine phospholipases C and D gene families and monitored fatty acid modulation during infection. Our results indicate that both susceptible and resistant grapevine hosts did not present wide fatty acid or gene expression modulation. The modulation of genes associated with lipid signalling and fatty acids seems to be specific to Regent, which raises the hypothesis of being specifically linked to the Rpv3 loci. In Sauvignac, the Rpv12 may be dominant concerning the defence response, and, thus, this genotype may present the activation of other pathways rather than lipid signalling. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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22. Anti-Inflammatory Effect of Specialized Proresolving Lipid Mediators on Mesenchymal Stem Cells: An In Vitro Study.
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AlZahrani, Shahd, Shinwari, Zakia, Gaafar, Ameera, Alaiya, Ayodele, and Al-Kahtani, Ahmed
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MESENCHYMAL stem cells , *INFLAMMATORY mediators , *STEM cells , *PEPTIDES , *LIPIDS , *WESTERN immunoblotting - Abstract
An interconnection between tissue inflammation and regeneration has been established through the regulation of defense and repair mechanisms within diseased dental tissue triggered by the release of immune-resolvent mediators. To better our understanding of the role of specific pro-resolving mediators (SPMs) in inflamed human bone marrow-derived mesenchymal stem cells (hBMMSCs), we studied the effects of Resolvin E1 (RvE1) and Maresin 1 (MaR1) in lipopoly-saccharide (LPS) stimulated hBMMSCs. The hBMMSCs were divided into five different groups, each of which was treated with or without SPMs. Group-1: negative control (no LPS stimulation), Group-2: positive control (LPS-stimulated), Group-3: RvE1 100 nM + 1 μg/mL LPS, Group-4: MaR1 100 nM + 1 µg/mL LPS, and Group-5: RvE1 100 nM + MaR1100 nM + 1 μg/mL LPS. Cell proliferation, apoptosis, migration, colony formation, Western blotting, cytokine array, and LC/MS analysis were all performed on each group to determine the impact of SPMs on inflammatory stem cells. According to our data, RvE1 plus MaR1 effectively reduced inflammation in hBMMSCs. In particular, IL-4, 1L-10, and TGF-β1 activation and downregulation of RANKL, TNF-α, and IFN-γ compared to groups receiving single SPM were shown to be significantly different (Group 3 and 4). In addition, the LC/MS analysis revealed the differentially regulated peptide's role in immunological pathways that define the cellular state against inflammation. Inflamed hBMMSCs treated with a combination of Resolvin E1 (RvE1) and Maresin 1 (MaR1) promoted the highest inflammatory resolution compared to the other groups; this finding suggests a potential new approach of treating bacterially induced dental infections. [ABSTRACT FROM AUTHOR]
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- 2023
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23. PCSK9 in Liver Cancers at the Crossroads between Lipid Metabolism and Immunity.
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Alannan, Malak, Seidah, Nabil G., and Merched, Aksam J.
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LIPID metabolism , *LOW density lipoprotein receptors , *LIVER cancer , *CELL receptors , *MAJOR histocompatibility complex , *LIPIDS , *METABOLISM - Abstract
Metabolic rewiring and defective immune responses are considered to be the main driving forces sustaining cell growth and oncogenesis in many cancers. The atypical enzyme, proprotein convertase subtilisin/kexin type 9 (PCSK9), is produced by the liver in large amounts and plays a major role in lipid metabolism via the control of the low density lipoprotein receptor (LDLR) and other cell surface receptors. In this context, many clinical studies have clearly demonstrated the high efficacy of PCSK9 inhibitors in treating hyperlipidemia and cardiovascular diseases. Recent data implicated PCSK9 in the degradation of major histocompatibility complex I (MHC-I) receptors and the immune system as well as in other physiological activities. This review highlights the complex crosstalk between PCSK9, lipid metabolism and immunosuppression and underlines the latest advances in understanding the involvement of this convertase in other critical functions. We present a comprehensive assessment of the different strategies targeting PCSK9 and show how these approaches could be extended to future therapeutic options to treat cancers with a main focus on the liver. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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24. Lipid Polarization during Cytokinesis.
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Kunduri, Govind, Acharya, Usha, and Acharya, Jairaj K.
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CYTOKINESIS , *SPHINGOLIPIDS , *EUKARYOTIC cells , *NUMBERS of species , *LIPIDS , *CELL membranes - Abstract
The plasma membrane of eukaryotic cells is composed of a large number of lipid species that are laterally segregated into functional domains as well as asymmetrically distributed between the outer and inner leaflets. Additionally, the spatial distribution and organization of these lipids dramatically change in response to various cellular states, such as cell division, differentiation, and apoptosis. Division of one cell into two daughter cells is one of the most fundamental requirements for the sustenance of growth in all living organisms. The successful completion of cytokinesis, the final stage of cell division, is critically dependent on the spatial distribution and organization of specific lipids. In this review, we discuss the properties of various lipid species associated with cytokinesis and the mechanisms involved in their polarization, including forward trafficking, endocytic recycling, local synthesis, and cortical flow models. The differences in lipid species requirements and distribution in mitotic vs. male meiotic cells will be discussed. We will concentrate on sphingolipids and phosphatidylinositols because their transbilayer organization and movement may be linked via the cytoskeleton and thus critically regulate various steps of cytokinesis. [ABSTRACT FROM AUTHOR]
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- 2022
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25. Paraoxonase 2 (PON2) Deficiency Reproduces Lipid Alterations of Diabetic and Inflammatory Glomerular Disease and Affects TRPC6 Signaling.
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Hagmann, Henning, Khayyat, Naghmeh Hassanzadeh, Oezel, Cem, Papadakis, Antonios, Kuczkowski, Alexander, Benzing, Thomas, Gulbins, Erich, Dryer, Stuart, and Brinkkoetter, Paul T.
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KIDNEY glomerulus diseases , *PARAOXONASE , *CELLULAR signal transduction , *CELL communication , *KNOCKOUT mice , *LIPIDS , *DOXORUBICIN - Abstract
Diabetes and inflammatory diseases are associated with an altered cellular lipid composition due to lipid peroxidation. The pathogenic potential of these lipid alterations in glomerular kidney diseases remains largely obscure as suitable cell culture and animal models are lacking. In glomerular disease, a loss of terminally differentiated glomerular epithelial cells called podocytes refers to irreversible damage. Podocytes are characterized by a complex ramified cellular architecture and highly active transmembrane signaling. Alterations in lipid composition in states of disease have been described in podocytes but the pathophysiologic mechanisms mediating podocyte damage are unclear. In this study, we employ a genetic deletion of the anti-oxidative, lipid-modifying paraoxonase 2 enzyme (PON2) as a model to study altered cellular lipid composition and its effects on cellular signaling in glomerular disease. PON2 deficiency reproduces features of an altered lipid composition of glomerular disease, characterized by an increase in ceramides and cholesterol. PON2 knockout mice are more susceptible to glomerular damage in models of aggravated oxidative stress such as adriamycin-induced nephropathy. Voltage clamp experiments in cultured podocytes reveal a largely increased TRPC6 conductance after a membrane stretch in PON2 deficiency. Correspondingly, a concomitant knockout of TRPC6 and PON2 partially rescues the aggravated glomerular phenotype of a PON2 knockout in the adriamycin model. This study establishes PON2 deficiency as a model to investigate the pathophysiologic mechanisms of podocyte dysfunction related to alterations in the lipid composition, as seen in diabetic and inflammatory glomerular disease. Expanding the knowledge on these routes and options of intervention could lead to novel treatment strategies for glomerular disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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26. TFEB; Beyond Its Role as an Autophagy and Lysosomes Regulator.
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Franco-Juárez, Berenice, Coronel-Cruz, Cristina, Hernández-Ochoa, Beatriz, Gómez-Manzo, Saúl, Cárdenas-Rodríguez, Noemi, Arreguin-Espinosa, Roberto, Bandala, Cindy, Canseco-Ávila, Luis Miguel, and Ortega-Cuellar, Daniel
- Subjects
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POST-translational modification , *LYSOSOMES , *AUTOPHAGY , *CELLULAR aging , *DNA repair , *LIPID metabolism , *GENE expression - Abstract
Transcription factor EB (TFEB) is considered the master transcriptional regulator of autophagy and lysosomal biogenesis, which regulates target gene expression through binding to CLEAR motifs. TFEB dysregulation has been linked to the development of numerous pathological conditions; however, several other lines of evidence show that TFEB might be a point of convergence of diverse signaling pathways and might therefore modulate other important biological processes such as cellular senescence, DNA repair, ER stress, carbohydrates, and lipid metabolism and WNT signaling-related processes. The regulation of TFEB occurs predominantly at the post-translational level, including phosphorylation, acetylation, SUMOylating, PARsylation, and glycosylation. It is noteworthy that TFEB activation is context-dependent; therefore, its regulation is subjected to coordinated mechanisms that respond not only to nutrient fluctuations but also to stress cell programs to ensure proper cell homeostasis and organismal health. In this review, we provide updated insights into novel post-translational modifications that regulate TFEB activity and give an overview of TFEB beyond its widely known role in autophagy and the lysosomal pathway, thus opening the possibility of considering TFEB as a potential therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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27. Neuroprotective and Anti-Inflammatory Effects of Linoleic Acid in Models of Parkinson's Disease: The Implication of Lipid Droplets and Lipophagy.
- Author
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Alarcon-Gil, Jesus, Sierra-Magro, Ana, Morales-Garcia, Jose A., Sanz-SanCristobal, Marina, Alonso-Gil, Sandra, Cortes-Canteli, Marta, Niso-Santano, Mireia, Martínez-Chacón, Guadalupe, Fuentes, Jose M., Santos, Angel, and Perez-Castillo, Ana
- Subjects
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PARKINSON'S disease , *ALZHEIMER'S disease , *LIPID metabolism , *LIPIDS , *NEUROPROTECTIVE agents , *LINOLEIC acid , *APOLIPOPROTEIN E4 - Abstract
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease. The principal pathological feature of PD is the progressive loss of dopaminergic neurons in the ventral midbrain. This pathology involves several cellular alterations: oxidative stress, mitochondrial dysfunction, loss of proteostasis, and autophagy impairment. Moreover, in recent years, lipid metabolism alterations have become relevant in PD pathogeny. The modification of lipid metabolism has become a possible way to treat the disease. Because of this, we analyzed the effect and possible mechanism of action of linoleic acid (LA) on an SH-SY5Y PD cell line model and a PD mouse model, both induced by 6-hydroxydopamine (6-OHDA) treatment. The results show that LA acts as a potent neuroprotective and anti-inflammatory agent in these PD models. We also observed that LA stimulates the biogenesis of lipid droplets and improves the autophagy/lipophagy flux, which resulted in an antioxidant effect in the in vitro PD model. In summary, we confirmed the neuroprotective effect of LA in vitro and in vivo against PD. We also obtained some clues about the novel neuroprotective mechanism of LA against PD through the regulation of lipid droplet dynamics. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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28. Endothelial Barrier Disruption by Lipid Emulsions Containing a High Amount of N3 Fatty Acids (Omegaven) but Not N6 Fatty Acids (Intralipid).
- Author
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Gueguen, Emilie, Morsy, Yasser, Scharl, Michael, Krämer, Stefanie D., Zaugg, Michael, Hersberger, Martin, Rogler, Gerhard, and Wawrzyniak, Marcin
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FATTY acids , *ESSENTIAL fatty acids , *EMULSIONS , *LIPIDS , *ENDOTHELIAL cells , *PARENTERAL feeding - Abstract
Lipid emulsions are crucial for life-saving total parenteral nutrition (TPN). Their composition provides a high amount of essential fatty acids and calories for millions of patients with serious diseases. Nevertheless, several TPN-mediated side-effects have been reported in over 90% of patients. This project aimed to investigate the effect of a high amount of ω3 fatty acids (Omegaven®) emulsion vs. a high amount of ω6 fatty acids (Intralipid®) emulsions on the endothelial barrier function. EA.hy926 cell line was cultured and incubated with 0.01, 0.1, and 1 mM lipid emulsions. The influence of these lipid emulsions on the barrier function was assessed using ECIS technology, immunofluorescent microscopy, viability measurements by flow cytometry, multiplex cytokines analysis, and qRT-PCR. BODIPY staining confirmed the uptake of fatty acids by endothelial cells. ECIS measurements demonstrated that a high concentration of Omegaven® prevents barrier formation and impairs the barrier function by inducing cell detachment. Moreover, the expression of VE-cadherin and F-actin formation showed a reorganization of the cell structure within 2 h of 1 mM Omegaven® addition. Interestingly, the study's findings contradict previous studies and revealed that Omegaven® at high concentration, but not Intralipid, induces cell detachments, impairing endothelial cells' barrier function. In summary, our studies shed new light on the effect of lipid emulsions on the endothelium. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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29. The Nuclear Pore Complex: Birth, Life, and Death of a Cellular Behemoth.
- Author
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Dultz, Elisa, Wojtynek, Matthias, Medalia, Ohad, and Onischenko, Evgeny
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EUKARYOTIC cells , *NUCLEOPORINS , *NUCLEAR membranes , *MEMBRANE fusion , *INVENTORIES - Abstract
Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500–1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. There are a number of as yet unresolved questions about how the versatility of NPC assembly and composition is established, how cells monitor the functional state of NPCs or how they could be renewed. Here, we review current progress in our understanding of the key aspects of NPC architecture and lifecycle. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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30. Insight into Extracellular Vesicle-Cell Communication: From Cell Recognition to Intracellular Fate.
- Author
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Ginini, Lana, Billan, Salem, Fridman, Eran, and Gil, Ziv
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CELLULAR recognition , *CELL communication , *CELL anatomy , *EXTRACELLULAR vesicles , *APOPTOTIC bodies , *EXOSOMES - Abstract
Extracellular vesicles (EVs) are heterogamous lipid bilayer-enclosed membranous structures secreted by cells. They are comprised of apoptotic bodies, microvesicles, and exosomes, and carry a range of nucleic acids and proteins that are necessary for cell-to-cell communication via interaction on the cells surface. They initiate intracellular signaling pathways or the transference of cargo molecules, which elicit pleiotropic responses in recipient cells in physiological processes, as well as pathological processes, such as cancer. It is therefore important to understand the molecular means by which EVs are taken up into cells. Accordingly, this review summarizes the underlying mechanisms involved in EV targeting and uptake. The primary method of entry by EVs appears to be endocytosis, where clathrin-mediated, caveolae-dependent, macropinocytotic, phagocytotic, and lipid raft-mediated uptake have been variously described as being prevalent. EV uptake mechanisms may depend on proteins and lipids found on the surfaces of both vesicles and target cells. As EVs have been shown to contribute to cancer growth and progression, further exploration and targeting of the gateways utilized by EVs to internalize into tumor cells may assist in the prevention or deceleration of cancer pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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31. Multi-Fold Enhancement of Tocopherol Yields Employing High CO 2 Supplementation and Nitrate Limitation in Native Isolate Monoraphidium sp.
- Author
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Singh, Rabinder, Nesamma, Asha Arumugam, Narula, Alka, and Jutur, Pannaga Pavan
- Subjects
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VITAMIN E , *CARBON dioxide , *GAS chromatography/Mass spectrometry (GC-MS) , *DIETARY supplements , *GABA - Abstract
Tocopherols are the highly active form of the antioxidant molecules involved in scavenging of free radicals and protect the cell membranes from reactive oxygen species (ROS). In the present study, we focused on employing carbon supplementation with varying nitrate concentrations to enhance the total tocopherol yields in the native isolate Monoraphidium sp. CABeR41. The total tocopherol productivity of NRHC (Nitrate replete + 3% CO2) supplemented was (306.14 µg·L−1 d−1) which was nearly 2.5-fold higher compared to NRVLC (Nitrate replete + 0.03% CO2) (60.35 µg·L−1 d−1). The best tocopherol productivities were obtained in the NLHC (Nitrate limited + 3% CO2) supplemented cells (734.38 µg·L−1 d−1) accompanied by a significant increase in cell biomass (2.65-fold) and total lipids (6.25-fold). Further, global metabolomics using gas chromatography-mass spectrometry (GC-MS) was done in the defined conditions to elucidate the molecular mechanism during tocopherol accumulation. In the present study, the Monoraphidium sp. responded to nitrogen limitation by increase in nitrogen assimilation, with significant upregulation in gamma-Aminobutyric acid (GABA). Moreover, the tricarboxylic acid (TCA) cycle upregulation depicted increased availability of carbon skeletons and reducing power, which is leading to increased biomass yields along with the other biocommodities. In conclusion, our study depicts valorization of carbon dioxide as a cost-effective alternative for the enhancement of biomass along with tocopherols and other concomitant products like lipids and carotenoids in the indigenous strain Monoraphidium sp., as an industrial potential strain with relevance in nutraceuticals and pharmaceuticals. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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32. GBA Variants and Parkinson Disease: Mechanisms and Treatments.
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Smith, Laura and Schapira, Anthony H. V.
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LYSOSOMES , *PARKINSON'S disease , *UNFOLDED protein response , *THERAPEUTICS , *DISEASE risk factors , *LIPID metabolism - Abstract
The GBA gene encodes for the lysosomal enzyme glucocerebrosidase (GCase), which maintains glycosphingolipid homeostasis. Approximately 5–15% of PD patients have mutations in the GBA gene, making it numerically the most important genetic risk factor for Parkinson disease (PD). Clinically, GBA-associated PD is identical to sporadic PD, aside from the earlier age at onset (AAO), more frequent cognitive impairment and more rapid progression. Mutations in GBA can be associated with loss- and gain-of-function mechanisms. A key hallmark of PD is the presence of intraneuronal proteinaceous inclusions named Lewy bodies, which are made up primarily of alpha-synuclein. Mutations in the GBA gene may lead to loss of GCase activity and lysosomal dysfunction, which may impair alpha-synuclein metabolism. Models of GCase deficiency demonstrate dysfunction of the autophagic-lysosomal pathway and subsequent accumulation of alpha-synuclein. This dysfunction can also lead to aberrant lipid metabolism, including the accumulation of glycosphingolipids, glucosylceramide and glucosylsphingosine. Certain mutations cause GCase to be misfolded and retained in the endoplasmic reticulum (ER), activating stress responses including the unfolded protein response (UPR), which may contribute to neurodegeneration. In addition to these mechanisms, a GCase deficiency has also been associated with mitochondrial dysfunction and neuroinflammation, which have been implicated in the pathogenesis of PD. This review discusses the pathways associated with GBA-PD and highlights potential treatments which may act to target GCase and prevent neurodegeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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33. Imaging Endocannabinoids and Bioactive Lipid Messengers in Basic Research and Biomedical Application.
- Author
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Aoki, Jun and Isokawa, Masako
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CANNABINOIDS , *LIPIDS , *CANNABINOID receptors , *MEDICAL research - Abstract
In addition, Raman microscopy [[3]], vibrational spectroscopy [[4]], and lipophilic fluorescent indicators [[5]] make unique contributions in locating eCBs and other signaling lipids. In order to visualize individual lipid molecules, the high-resolution single-cell imaging technique, which comprises a new laser assembly and novel ion optics, has emerged to complement the insufficient spatial resolution typically found in conventional IMS equipment [[2]]. Endocannabinoids (eCBs) are representative bioactive lipid messengers. [Extracted from the article]
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- 2022
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34. Generating Membrane Curvature at the Nuclear Pore: A Lipid Point of View.
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Peeters, Bas W. A., Piët, Alexandra C. A., and Fornerod, Maarten
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NUCLEAR membranes , *LIPID metabolism , *NUCLEAR shapes , *EUKARYOTIC cells , *CYTOPLASM - Abstract
In addition to its structural role in enclosing and protecting the genome, the nuclear envelope (NE) forms a highly adaptive communication interface between the cytoplasm and the nuclear interior in eukaryotic cells. The double membrane of the NE is perforated by nuclear pores lined with large multi-protein structures, called nuclear-pore complexes (NPCs), which selectively allow the bi-directional transport of ions and macromolecular cargo. In order to nucleate a pore, the inner and outer nuclear membrane have to fuse at the site of NPC insertion, a process requiring both lipid bilayers to be deformed into highly curved structures. How this curvature is achieved and which factors are involved in inducing and stabilizing membrane curvature at the nuclear pore remain largely unclear. In this review, we will summarize the molecular mechanisms thought to be involved in membrane curvature generation, with a particular emphasis on the role of lipids and lipid metabolism in shaping the nuclear pore membrane. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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35. Reprogramming of Lipid Metabolism in Lung Cancer: An Overview with Focus on EGFR-Mutated Non-Small Cell Lung Cancer.
- Author
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Eltayeb, Kamal, La Monica, Silvia, Tiseo, Marcello, Alfieri, Roberta, and Fumarola, Claudia
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NON-small-cell lung carcinoma , *LIPID metabolism , *LUNG cancer , *LIPIDS - Abstract
Lung cancer is the leading cause of cancer deaths worldwide. Most of lung cancer cases are classified as non-small cell lung cancers (NSCLC). EGFR has become an important therapeutic target for the treatment of NSCLC patients, and inhibitors targeting the kinase domain of EGFR are currently used in clinical settings. Recently, an increasing interest has emerged toward understanding the mechanisms and biological consequences associated with lipid reprogramming in cancer. Increased uptake, synthesis, oxidation, or storage of lipids has been demonstrated to contribute to the growth of many types of cancer, including lung cancer. In this review, we provide an overview of metabolism in cancer and then explore in more detail the role of lipid metabolic reprogramming in lung cancer development and progression and in resistance to therapies, emphasizing its connection with EGFR signaling. In addition, we summarize the potential therapeutic approaches targeting lipid metabolism for lung cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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36. Long-Term High-Fat Diet Consumption Depletes Glial Cells and Tyrosine Hydroxylase–Containing Neurons in the Brain of Middle-Aged Rats.
- Author
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Chou, Mei-Chuan, Lee, Hsiang-Chun, Liu, Yen-Chin, Yen, Patrick Szu-Ying, Liu, Ching-Kuan, Chen, Chu-Huang, Hsieh, Tzu-Han, and Chen, Shiou-Lan
- Subjects
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NEUROGLIA , *HIGH-fat diet , *NEURONS , *TYROSINE , *OLDER people , *LOCUS coeruleus - Abstract
Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of neuronal degeneration. However, the effects of chronic dyslipidemia on brain function, especially in older individuals, remain unclear. In this study, middle-aged 37-week-old male Wistar-Kyoto rats were fed a normal diet (ND) or a 45% high-fat diet (HFD) for 30 weeks (i.e., until 67 weeks of age). To study the effects of chronic dyslipidemia on the brain, we analyzed spontaneous locomotor activity, cognitive function, and brain tissues in both groups of rats after 30 weeks. Compared with age-matched rats fed a ND, Wistar-Kyoto rats fed a HFD had dyslipidemia and showed decreased movement but normal recognition of a novel object. In our brain analyses, we observed a significant decrease in astrocytes and tyrosine hydroxylase–containing neurons in the substantia nigra and locus coeruleus of rats fed a HFD compared with rats fed a ND. However, hippocampal pyramidal neurons were not affected. Our findings indicate that the long-term consumption of a HFD may cause lipid metabolism overload in the brain and damage to glial cells. The decrease in astrocytes may lead to reduced protection of the brain and affect the survival of tyrosine hydroxylase–containing neurons but not pyramidal neurons of the hippocampus. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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37. Komagataella phaffii Cue5 Piggybacks on Lipid Droplets for Its Vacuolar Degradation during Stationary Phase Lipophagy.
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Kumar, Ravinder, Shroff, Ankit, and Nazarko, Taras Y.
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PICHIA pastoris , *SCAFFOLD proteins , *LIPIDS , *AUTOPHAGY , *YEAST - Abstract
Recently, we developed Komagataella phaffii (formerly Pichia pastoris) as a model for lipophagy, the selective autophagy of lipid droplets (LDs). We found that lipophagy pathways induced by acute nitrogen (N) starvation and in stationary (S) phase have different molecular mechanisms. Moreover, both types of lipophagy are independent of Atg11, the scaffold protein that interacts with most autophagic receptors and, therefore, is essential for most types of selective autophagy in yeast. Since yeast aggrephagy, the selective autophagy of ubiquitinated protein aggregates, is also independent of Atg11 and utilizes the ubiquitin-binding receptor, Cue5, we studied the relationship of K. phaffii Cue5 with differentially induced LDs and lipophagy. While there was no relationship of Cue5 with LDs and lipophagy under N-starvation conditions, Cue5 accumulated on LDs in S-phase and degraded together with LDs via S-phase lipophagy. The accumulation of Cue5 on LDs and its degradation by S-phase lipophagy strongly depended on the ubiquitin-binding CUE domain and Prl1, the positive regulator of lipophagy 1. However, unlike Prl1, which is required for S-phase lipophagy, Cue5 was dispensable for it suggesting that Cue5 is rather a new substrate of this pathway. We propose that a similar mechanism (Prl1-dependent accumulation on LDs) might be employed by Prl1 to recruit another ubiquitin-binding protein that is essential for S-phase lipophagy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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38. 7-Ketocholesterol Induces Lipid Metabolic Reprogramming and Enhances Cholesterol Ester Accumulation in Cardiac Cells.
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Cheng, Mei-Ling, Tang, Hsiang-Yu, Wu, Pei-Ting, Yang, Cheng-Hung, Lo, Chi-Jen, Lin, Jui-Fen, and Ho, Hung-Yao
- Subjects
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HEART cells , *CHOLESTERYL ester transfer protein , *CHOLESTEROL , *LIPID metabolism , *LIPIDS , *ESTERS - Abstract
7-Ketocholesterol (7KCh) is a major oxidized cholesterol product abundant in lipoprotein deposits and atherosclerotic plaques. Our previous study has shown that 7KCh accumulates in erythrocytes of heart failure patients, and further investigation centered on how 7KCh may affect metabolism in cardiomyocytes. We applied metabolomics to study the metabolic changes in cardiac cell line HL-1 after treatment with 7KCh. Mevalonic acid (MVA) pathway-derived metabolites, such as farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate, phospholipids, and triacylglycerols levels significantly declined, while the levels of lysophospholipids, such as lysophosphatidylcholines (lysoPCs) and lysophosphatidylethanolamines (lysoPEs), considerably increased in 7KCh-treated cells. Furthermore, the cholesterol content showed no significant change, but the production of cholesteryl esters was enhanced in the treated cells. To explore the possible mechanisms, we applied mRNA-sequencing (mRNA-seq) to study genes differentially expressed in 7KCh-treated cells. The transcriptomic analysis revealed that genes involved in lipid metabolic processes, including MVA biosynthesis and cholesterol transport and esterification, were differentially expressed in treated cells. Integrated analysis of both metabolomic and transcriptomic data suggests that 7KCh induces cholesteryl ester accumulation and reprogramming of lipid metabolism through altered transcription of such genes as sterol O-acyltransferase- and phospholipase A2-encoding genes. The 7KCh-induced reprogramming of lipid metabolism in cardiac cells may be implicated in the pathogenesis of cardiovascular diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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39. A Novel Boron Lipid to Modify Liposomal Surfaces for Boron Neutron Capture Therapy.
- Author
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Shirakawa, Makoto, Zaboronok, Alexander, Nakai, Kei, Sato, Yuhki, Kayaki, Sho, Sakai, Tomonori, Tsurubuchi, Takao, Yoshida, Fumiyo, Nishiyama, Takashi, Suzuki, Minoru, Tomida, Hisao, and Matsumura, Akira
- Subjects
- *
BORON-neutron capture therapy , *NEUTRON capture , *BILAYER lipid membranes , *LIPIDS , *BORON , *POLYETHYLENE glycol - Abstract
Boron neutron capture therapy (BNCT) is a cancer treatment with clinically demonstrated efficacy using boronophenylalanine (BPA) and sodium mercaptododecaborate (BSH). However, tumor tissue selectivity of BSH and retention of BPA in tumor cells is a constant problem. To ensure boron accumulation and retention in tumor tissues, we designed a novel polyethylene glycol (PEG)-based boron-containing lipid (PBL) and examined the potency of delivery of boron using novel PBL-containing liposomes, facilitated by the enhanced permeability and retention (EPR) effect. PBL was synthesized by the reaction of distearoylphosphoethanolamine and BSH linked by PEG with Michael addition while liposomes modified using PBL were prepared from the mixed lipid at a constant molar ratio. In this manner, novel boron liposomes featuring BSH in the liposomal surfaces, instead of being encapsulated in the inner aqueous phase or incorporated in the lipid bilayer membrane, were prepared. These PBL liposomes also carry additional payload capacity for more boron compounds (or anticancer agents) in their inner aqueous phase. The findings demonstrated that PBL liposomes are promising candidates to effect suitable boron accumulation for BNCT. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
40. Activation Mechanisms of the VPS34 Complexes.
- Author
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Ohashi, Yohei
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- *
CELL survival , *RAPAMYCIN , *NEURODEGENERATION , *AUTOPHAGY - Abstract
Phosphatidylinositol-3-phosphate (PtdIns(3)P) is essential for cell survival, and its intracellular synthesis is spatially and temporally regulated. It has major roles in two distinctive cellular pathways, namely, the autophagy and endocytic pathways. PtdIns(3)P is synthesized from phosphatidylinositol (PtdIns) by PIK3C3C/VPS34 in mammals or Vps34 in yeast. Pathway-specific VPS34/Vps34 activity is the consequence of the enzyme being incorporated into two mutually exclusive complexes: complex I for autophagy, composed of VPS34/Vps34–Vps15/Vps15-Beclin 1/Vps30-ATG14L/Atg14 (mammals/yeast), and complex II for endocytic pathways, in which ATG14L/Atg14 is replaced with UVRAG/Vps38 (mammals/yeast). Because of its involvement in autophagy, defects in which are closely associated with human diseases such as cancer and neurodegenerative diseases, developing highly selective drugs that target specific VPS34/Vps34 complexes is an essential goal in the autophagy field. Recent studies on the activation mechanisms of VPS34/Vps34 complexes have revealed that a variety of factors, including conformational changes, lipid physicochemical parameters, upstream regulators, and downstream effectors, greatly influence the activity of these complexes. This review summarizes and highlights each of these influences as well as clarifying key questions remaining in the field and outlining future perspectives. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
41. Decoupled Glucose and Lipid Metabolic Recovery after Viral Clearance in Direct-Acting Antiviral-Treated HCV Patients: A 3-Year Prospective Cohort Study.
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Lee, Heng, Chien, Rong-Nan, Pao, Li-Heng, Kuo, Chia-Jung, Huang, Po-Han, and Chang, Ming-Ling
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HDL cholesterol , *LIPIDS , *INSULIN resistance , *COHORT analysis , *HEPATITIS C virus , *LONGITUDINAL method , *CHOLESTERYL ester transfer protein - Abstract
Background/Aim: The recovery pattern of hepatitis C virus (HCV)-associated metabolic alteration after sustained virological response (SVR) following direct-acting antivirals (DAAs) remains elusive. Methods: A prospective cohort study of chronic HCV-infected (CHC) patients (n = 415) receiving DAAs (n = 365) was conducted. Metabolic profiles were examined in SVR patients (n = 360) every 3–6 months after therapy and compared with those of sex- and age-matched controls (n = 470). Results: At baseline, of 415, 168 (40.5%) had insulin resistance (IR). The following were associated: levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), HCV RNA, fibrosis-4 score, and interferon-λ3-rs12979860 genotype with total cholesterol (TC) levels; and TG levels and BMI with HOMA-IR. Over a 3-year follow-up, in SVR patients, BMI and TC levels and TG/HDL-C ratios increased from baseline, while HOMA-IR trended downward by 72 weeks after therapy and then increased. The increased HDL-C levels began to decrease after 72 weeks after therapy. TC and HOMA-IR were negatively associated with each other until 24 weeks after therapy. Earlier increases in BMI and decreases in HOMA-IR were noted in SVR patients with than in those without baseline IR. Compared with controls, in the subgroup without baseline IR, SVR patients had increased BMI and HOMA-IR levels. Metabolic profiles were similar between SVR patients and controls in the subgroup with baseline IR. Conclusions: In SVR patients treated with DAAs, the recovery of altered lipid and glucose metabolism was not coupled until 72-week post-therapy, when HOMA-IR reached its nadir. SVR patients with baseline IR recovered from HCV-associated metabolic alterations earlier than those without baseline IR. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
42. CFTR Protein: Not Just a Chloride Channel?
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Hanssens, Laurence S., Duchateau, Jean, and Casimir, Georges J.
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- *
CHLORIDE channels , *CYSTIC fibrosis transmembrane conductance regulator , *ION channels , *EXOCRINE pancreatic insufficiency , *ION transport (Biology) , *MUCOCILIARY system - Abstract
Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in a gene encoding a protein called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The CFTR protein is known to acts as a chloride (Cl−) channel expressed in the exocrine glands of several body systems where it also regulates other ion channels, including the epithelial sodium (Na+) channel (ENaC) that plays a key role in salt absorption. This function is crucial to the osmotic balance of the mucus and its viscosity. However, the pathophysiology of CF is more challenging than a mere dysregulation of epithelial ion transport, mainly resulting in impaired mucociliary clearance (MCC) with consecutive bronchiectasis and in exocrine pancreatic insufficiency. This review shows that the CFTR protein is not just a chloride channel. For a long time, research in CF has focused on abnormal Cl− and Na+ transport. Yet, the CFTR protein also regulates numerous other pathways, such as the transport of HCO3−, glutathione and thiocyanate, immune cells, and the metabolism of lipids. It influences the pH homeostasis of airway surface liquid and thus the MCC as well as innate immunity leading to chronic infection and inflammation, all of which are considered as key pathophysiological characteristics of CF. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
43. Plasma Membrane Fluidity: An Environment Thermal Detector in Plants.
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Cano-Ramirez, Dora L., Carmona-Salazar, Laura, Morales-Cedillo, Francisco, Ramírez-Salcedo, Jorge, Cahoon, Edgar B., and Gavilanes-Ruíz, Marina
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CELL membranes , *SESSILE organisms , *FLUORESCENT probes , *TEMPERATURE detectors , *PHASE transitions - Abstract
The lipid matrix in cell membranes is a dynamic, bidimensional array of amphipathic molecules exhibiting mesomorphism, which contributes to the membrane fluidity changes in response to temperature fluctuation. As sessile organisms, plants must rapidly and accurately respond to environmental thermal variations. However, mechanisms underlying temperature perception in plants are poorly understood. We studied the thermal plasticity of membrane fluidity using three fluorescent probes across a temperature range of −5 to 41 °C in isolated microsomal fraction (MF), vacuolar membrane (VM), and plasma membrane (PM) vesicles from Arabidopsis plants. Results showed that PM were highly fluid and exhibited more phase transitions and hysteresis, while VM and MF lacked such attributes. These findings suggest that PM is an important cell hub with the capacity to rapidly undergo fluidity modifications in response to small changes of temperatures in ranges spanning those experienced in natural habitats. PM fluidity behaves as an ideal temperature detector: it is always present, covers the whole cell, responds quickly and with sensitivity to temperature variations, functions with a cell free-energy cost, and it is physically connected with potential thermal signal transducers to elicit a cell response. It is an optimal alternative for temperature detection selected for the plant kingdom. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
44. Effect of Perioperative Lipid Status on Clinical Outcomes after Cardiac Surgery.
- Author
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Mihalj, Maks, Heinisch, Paul Philipp, Huber, Markus, Schefold, Joerg C., Hartmann, Alexander, Walter, Michael, Steinhagen-Thiessen, Elisabeth, Schmidli, Juerg, Stüber, Frank, Räber, Lorenz, and Luedi, Markus M.
- Subjects
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CARDIAC surgery , *TREATMENT effectiveness , *BLOOD lipids , *CARDIOPULMONARY bypass , *HDL cholesterol , *LIPIDS - Abstract
Patients undergoing cardiac surgery are at increased cardiovascular risk, which includes altered lipid status. However, data on the effect of cardiac surgery and cardiopulmonary bypass (CPB) on plasma levels of key lipids are scarce. We investigated potential effects of CPB on plasma lipid levels and associations with early postoperative clinical outcomes. This is a prospective bio-bank study of patients undergoing elective cardiac surgery at our center January to December 2019. The follow-up period was 1 year after surgery. Blood sampling was performed before induction of general anesthesia, upon weaning from cardiopulmonary bypass (CPB), and on the first day after surgery. Clinical end points included the incidence of postoperative stroke, myocardial infarction, and death of any cause at 30 days after surgery as well as 1-year all-cause mortality. A total of 192 cardiac surgery patients (75% male, median age 67.0 years (interquartile range 60.0–73.0), median BMI 26.1 kg/m2 (23.7–30.4)) were included. A significant intraoperative decrease in plasma levels compared with preoperative levels (all p < 0.0001) was observed for total cholesterol (TC) (Cliff's delta d: 0.75 (0.68–0.82; 95% CI)), LDL-Cholesterol (LDL-C) (d: 0.66 (0.57–0.73)) and HDL-Cholesterol (HDL-C) (d: 0.72 (0.64–0.79)). At 24h after surgery, the plasma levels of LDL-C (d: 0.73 (0.650.79)) and TC (d: 0.77 (0.69–0.82)) continued to decrease compared to preoperative levels, while the plasma levels of HDL-C (d: 0.46 (0.36–0.55)) and TG (d: 0.40 (0.29–0.50)) rebounded, but all remained below the preoperative levels (p < 0.001). Mortality at 30 days was 1.0% (N = 2/192), and 1-year mortality was 3.8% (N = 7/186). Postoperative myocardial infarction occurred in 3.1% of patients (N = 6/192) and postoperative stroke in 5.8% (N = 11/190). Adjusting for age, sex, BMI, and statin therapy, we noted a protective effect of postoperative occurrence of stroke for pre-to-post-operative changes in TC (adjusted odds ratio (OR) 0.29 (0.07–0.90), p = 0.047), in LDL-C (aOR 0.19 (0.03–0.88), p = 0.045), and in HDL-C (aOR 0.01 (0.00–0.78), p = 0.039). No associations were observed between lipid levels and 1-year mortality. In conclusion, cardiac surgery induces a significant sudden drop in levels of key plasma lipids. This effect was pronounced during the operation, and levels remained significantly lowered at 24 h after surgery. The intraoperative drops in LDL-C, TC, and HDL-C were associated with a protective effect against occurrence of postoperative stroke in adjusted models. We demonstrate that the changes in key plasma lipid levels during surgery are strongly correlated, which makes attributing the impact of each lipid to the clinical end points, such as postoperative stroke, a challenging task. Large-scale analyses should investigate additional clinical outcome measures. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Towards Understanding the Direct and Indirect Actions of Growth Hormone in Controlling Hepatocyte Carbohydrate and Lipid Metabolism.
- Author
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Vázquez-Borrego, Mari C., del Rio-Moreno, Mercedes, and Kineman, Rhonda D.
- Subjects
- *
SOMATOTROPIN , *CARBOHYDRATE metabolism , *LIPID metabolism , *DIRECT action , *SOMATOMEDIN C , *METABOLIC regulation - Abstract
Growth hormone (GH) is critical for achieving normal structural growth. In addition, GH plays an important role in regulating metabolic function. GH acts through its GH receptor (GHR) to modulate the production and function of insulin-like growth factor 1 (IGF1) and insulin. GH, IGF1, and insulin act on multiple tissues to coordinate metabolic control in a context-specific manner. This review will specifically focus on our current understanding of the direct and indirect actions of GH to control liver (hepatocyte) carbohydrate and lipid metabolism in the context of normal fasting (sleep) and feeding (wake) cycles and in response to prolonged nutrient deprivation and excess. Caveats and challenges related to the model systems used and areas that require further investigation towards a clearer understanding of the role GH plays in metabolic health and disease are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
46. Assessment of Nitrate Removal Capacity of Two Selected Eukaryotic Green Microalgae.
- Author
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Rani, Vaishali and Maróti, Gergely
- Subjects
- *
MICROALGAE , *CHLAMYDOMONAS , *NITRATES , *SODIUM nitrate , *BODIES of water , *LEAD in water - Abstract
Eutrophication is a leading problem in water bodies all around the world in which nitrate is one of the major contributors. The present study was conducted to study the effects of various concentrations of nitrate on two eukaryotic green microalgae, Chlamydomonas sp. MACC-216 and Chlorella sp. MACC-360. For this purpose, both microalgae were grown in a modified tris-acetate-phosphate medium (TAP-M) with three different concentrations of sodium nitrate, i.e., 5 mM (TAP-M5), 10 mM (TAP-M10) and 15 mM (TAP-M15), for 6 days and it was observed that both microalgae were able to remove nitrate completely from the TAP-M5 medium. Total amount of pigments decreased with the increasing concentration of nitrate, whereas protein and carbohydrate contents remained unaffected. High nitrate concentration (15 mM) led to an increase in lipids in Chlamydomonas sp. MACC-216, but not in Chlorella sp. MACC-360. Furthermore, Chlamydomonas sp. MACC-216 and Chlorella sp. MACC-360 were cultivated for 6 days in synthetic wastewater (SWW) with varying concentrations of nitrate where both microalgae grew well and showed an adequate nitrate removal capacity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
47. Alpha-Synuclein and Lipids: The Elephant in the Room?
- Author
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Sarchione, Alessia, Marchand, Antoine, Taymans, Jean-Marc, and Chartier-Harlin, Marie-Christine
- Subjects
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LIPID metabolism , *ALPHA-synuclein , *PARKINSON'S disease , *MEMBRANE lipids , *HOMEOSTASIS - Abstract
Since the initial identification of alpha-synuclein (α-syn) at the synapse, numerous studies demonstrated that α-syn is a key player in the etiology of Parkinson's disease (PD) and other synucleinopathies. Recent advances underline interactions between α-syn and lipids that also participate in α-syn misfolding and aggregation. In addition, increasing evidence demonstrates that α-syn plays a major role in different steps of synaptic exocytosis. Thus, we reviewed literature showing (1) the interplay among α-syn, lipids, and lipid membranes; (2) advances of α-syn synaptic functions in exocytosis. These data underscore a fundamental role of α-syn/lipid interplay that also contributes to synaptic defects in PD. The importance of lipids in PD is further highlighted by data showing the impact of α-syn on lipid metabolism, modulation of α-syn levels by lipids, as well as the identification of genetic determinants involved in lipid homeostasis associated with α-syn pathologies. While questions still remain, these recent developments open the way to new therapeutic strategies for PD and related disorders including some based on modulating synaptic functions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
48. Role of ERLINs in the Control of Cell Fate through Lipid Rafts.
- Author
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Manganelli, Valeria, Longo, Agostina, Mattei, Vincenzo, Recalchi, Serena, Riitano, Gloria, Caissutti, Daniela, Capozzi, Antonella, Sorice, Maurizio, Misasi, Roberta, and Garofalo, Tina
- Subjects
- *
LIPID rafts , *ENDOPLASMIC reticulum , *LIPID metabolism , *METABOLIC regulation , *PROTEOLYSIS , *GLYCOPROTEINS , *LIPIDS , *RYANODINE receptors - Abstract
ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They are generally localized in the endoplasmic reticulum (ER), where ERLIN1 forms a heteroligomeric complex with its closely related ERLIN2. Well-defined functions of ERLINS are promotion of ER-associated protein degradation, mediation of inositol 1,4,5-trisphosphate (IP3) receptors, processing and regulation of lipid metabolism. Until now, ERLINs have been exclusively considered protein markers of ER lipid raft-like microdomains. However, under pathophysiological conditions, they have been described within mitochondria-associated endoplasmic reticulum membranes (MAMs), tethering sites between ER and mitochondria, characterized by the presence of specialized raft-like subdomains enriched in cholesterol and gangliosides, which play a key role in the membrane scrambling and function. In this context, it is emerging that ER lipid raft-like microdomains proteins, i.e., ERLINs, may drive mitochondria-ER crosstalk under both physiological and pathological conditions by association with MAMs, regulating the two main processes underlined, survival and death. In this review, we describe the role of ERLINs in determining cell fate by controlling the "interchange" between apoptosis and autophagy pathways, considering that their alteration has a significant impact on the pathogenesis of several human diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
49. Lipid Polymorphism of the Subchloroplast—Granum and Stroma Thylakoid Membrane–Particles. II. Structure and Functions.
- Author
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Dlouhý, Ondřej, Karlický, Václav, Arshad, Rameez, Zsiros, Ottó, Domonkos, Ildikó, Kurasová, Irena, Wacha, András F., Morosinotto, Tomas, Bóta, Attila, Kouřil, Roman, Špunda, Vladimír, and Garab, Győző
- Subjects
- *
SMALL-angle X-ray scattering , *CHLOROPHYLL spectra , *CIRCULAR dichroism , *ELECTROCHROMIC effect , *MAGNETIZATION transfer , *EMISSION spectroscopy , *LIPIDS - Abstract
In Part I, by using 31P-NMR spectroscopy, we have shown that isolated granum and stroma thylakoid membranes (TMs), in addition to the bilayer, display two isotropic phases and an inverted hexagonal (HII) phase; saturation transfer experiments and selective effects of lipase and thermal treatments have shown that these phases arise from distinct, yet interconnectable structural entities. To obtain information on the functional roles and origin of the different lipid phases, here we performed spectroscopic measurements and inspected the ultrastructure of these TM fragments. Circular dichroism, 77 K fluorescence emission spectroscopy, and variable chlorophyll-a fluorescence measurements revealed only minor lipase- or thermally induced changes in the photosynthetic machinery. Electrochromic absorbance transients showed that the TM fragments were re-sealed, and the vesicles largely retained their impermeabilities after lipase treatments—in line with the low susceptibility of the bilayer against the same treatment, as reflected by our 31P-NMR spectroscopy. Signatures of HII-phase could not be discerned with small-angle X-ray scattering—but traces of HII structures, without long-range order, were found by freeze-fracture electron microscopy (FF-EM) and cryo-electron tomography (CET). EM and CET images also revealed the presence of small vesicles and fusion of membrane particles, which might account for one of the isotropic phases. Interaction of VDE (violaxanthin de-epoxidase, detected by Western blot technique in both membrane fragments) with TM lipids might account for the other isotropic phase. In general, non-bilayer lipids are proposed to play role in the self-assembly of the highly organized yet dynamic TM network in chloroplasts. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
50. Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans.
- Author
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Franco-Juárez, Berenice, Gómez-Manzo, Saúl, Hernández-Ochoa, Beatriz, Cárdenas-Rodríguez, Noemi, Arreguin-Espinosa, Roberto, Pérez de la Cruz, Verónica, and Ortega-Cuellar, Daniel
- Subjects
- *
CAENORHABDITIS elegans , *CARBOHYDRATES , *HIGH-carbohydrate diet , *SUPPLY & demand , *AGING - Abstract
Health and lifespan are influenced by dietary nutrients, whose balance is dependent on the supply or demand of each organism. Many studies have shown that an increased carbohydrate–lipid intake plays a critical role in metabolic dysregulation, which impacts longevity. Caenorhabditis elegans has been successfully used as an in vivo model to study the effects of several factors, such as genetic, environmental, diet, and lifestyle factors, on the molecular mechanisms that have been linked to healthspan, lifespan, and the aging process. There is evidence showing the causative effects of high glucose on lifespan in different diabetic models; however, the precise biological mechanisms affected by dietary nutrients, specifically carbohydrates and lipids, as well as their links with lifespan and longevity, remain unknown. Here, we provide an overview of the deleterious effects caused by high-carbohydrate and high-lipid diets, as well as the molecular signals that affect the lifespan of C. elegans; thus, understanding the detailed molecular mechanisms of high-glucose- and lipid-induced changes in whole organisms would allow the targeting of key regulatory factors to ameliorate metabolic disorders and age-related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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