24 results on '"Siculella, Luisa"'
Search Results
2. In silico evidence that substitution of glycine for valine (p.G8V) in a common variant of TMPRSS2 isoform 1 increases accessibility to an endocytic signal: Implication for SARS-cov-2 entry into host cells and susceptibility to COVID-19
- Author
-
Calcagnile, Matteo, Damiano, Fabrizio, Lobreglio, Giambattista, Siculella, Luisa, Bozzetti, Maria Pia, Forgez, Patricia, Malgoyre, Alexandra, Libert, Nicolas, Bucci, Cecilia, Alifano, Marco, and Alifano, Pietro
- Published
- 2024
- Full Text
- View/download PDF
3. Encapsulation of Lactobacillus kefiri in alginate microbeads using a double novel aerosol technique
- Author
-
Demitri, Christian, Lamanna, Leonardo, De Benedetto, Egidio, Damiano, Fabrizio, Cappello, Maria Stella, Siculella, Luisa, and Sannino, Alessandro
- Published
- 2017
- Full Text
- View/download PDF
4. WITHDRAWN: Interplay between non-coding RNA transcription, stringent phenotype and antibiotic production in Streptomyces
- Author
-
Pinatel, Eva, Calcagnile, Matteo, Talà, Adelfia, Damiano, Fabrizio, Siculella, Luisa, Peano, Clelia, De Benedetto, Giuseppe Egidio, Pennetta, Antonio, De Bellis, Gianluca, and Alifano, Pietro
- Published
- 2022
- Full Text
- View/download PDF
5. Mitochondrial proteome analysis reveals depression of the Ndufs3 subunit and activity of complex I in diabetic rat brain
- Author
-
Taurino, Federica, Stanca, Eleonora, Siculella, Luisa, Trentadue, Raffaella, Papa, Sergio, Zanotti, Franco, and Gnoni, Antonio
- Published
- 2012
- Full Text
- View/download PDF
6. Lipid accumulation stimulates the cap-independent translation of SREBP-1a mRNA by promoting hnRNP A1 binding to its 5′-UTR in a cellular model of hepatic steatosis.
- Author
-
Siculella, Luisa, Tocci, Romina, Rochira, Alessio, Testini, Mariangela, Gnoni, Antonio, and Damiano, Fabrizio
- Subjects
- *
FATTY liver , *LIPIDS , *BIOACCUMULATION , *STEROL regulatory element-binding proteins , *MESSENGER RNA , *RIBOSOMES , *LIVER cells - Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease characterized by accumulation of lipid droplets in hepatocytes. Enhanced release of non-esterified fatty acids from adipose tissue accounts for a remarkable fraction of accumulated lipids. However, the de novo lipogenesis (DNL) is also implicated in the etiology of the NAFLD. Sterol Regulatory Element-Binding Protein-1 (SREBP-1) is a transcription factor modulating the expression of several lipogenic enzymes. In the present study, in order to investigate the effect of lipid droplet accumulation on DNL, we used a cellular model of steatosis represented by HepG2 cells cultured in a medium supplemented with free oleic and palmitic fatty acids (FFAs). We report that FFA supplementation induces the expression of genes coding for enzymes involved in the DNL as well as for the transcription factor SREBP-1a. The SREBP-1a mRNA translation, dependent on an internal ribosome entry site (IRES), and the SREBP-1a proteolytic cleavage are activated by FFAs. Furthermore, FFA treatment enhances the expression and the nucleus-cytosolic shuttling of hnRNP A1, a trans-activating factor of SREBP-1a IRES. The binding of hnRNP A1 to the SREBP-1a IRES is also increased upon FFA supplementation. The relocation of hnRNP A1 and the consequent increase of SREBP-1a translation are dependent on the p38 MAPK signal pathway, which is activated by FFAs. By RNA interference approach, we demonstrate that hnRNP A1 is implicated in the FFA-induced expression of SREBP-1a and of its target genes as well as in the lipid accumulation in cells. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
7. Expression of citrate carrier gene is activated by ER stress effectors XBP1 and ATF6α, binding to an UPRE in its promoter.
- Author
-
Damiano, Fabrizio, Tocci, Romina, Gnoni, Gabriele Vincenzo, and Siculella, Luisa
- Abstract
The Unfolded Protein Response (UPR) is an intracellular signaling pathway which is activated when unfolded or misfolded proteins accumulate in the Endoplasmic Reticulum (ER), a condition commonly referred to as ER stress. It has been shown that lipid biosynthesis is increased in ER-stressed cells. The N ε -lysine acetylation of ER-resident proteins, including chaperones and enzymes involved in the post-translational protein modification and folding, occurs upon UPR activation. In both ER proteins acetylation and lipid synthesis, acetyl-CoA is the donor of acetyl group and it is transported from the cytosol into the ER. The cytosolic pool of acetyl-CoA is mainly derived from the activity of mitochondrial citrate carrier (CiC). Here, we have demonstrated that expression of CiC is activated in human HepG2 and rat BRL-3A cells during tunicamycin-induced ER stress. This occurs through the involvement of an ER stress responsive region identified within the human and rat CiC proximal promoter. A functional Unfolded Protein Response Element (UPRE) confers responsiveness to the promoter activation by UPR transducers ATF6α and XBP1. Overall, our data demonstrate that CiC expression is activated during ER stress through the binding of ATF6α and XBP1 to an UPRE element located in the proximal promoter of Cic gene. The role of ER stress-mediated induction of CiC expression has been discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
8. Extra virgin olive oil phenols down-regulate lipid synthesis in primary-cultured rat-hepatocytes.
- Author
-
Priore, Paola, Siculella, Luisa, and Gnoni, Gabriele Vincenzo
- Subjects
- *
THERAPEUTIC use of olive oil , *LIPID synthesis , *LIVER cells , *CELL culture , *LABORATORY rats , *HYDROXYTYROSOL , *TYROSOL , *GENETIC regulation - Abstract
Abstract: Hydroxytyrosol, tyrosol, and oleuropein, the main phenols present in extra virgin olive oil, have been reported to exert several biochemical and pharmacological effects. Here, we investigated the short-term effects of these compounds on lipid synthesis in primary-cultured rat-liver cells. Hydroxytyrosol, tyrosol and oleuropein inhibited both de novo fatty acid and cholesterol syntheses without an effect on cell viability. The inhibitory effect of individual compounds was already evident within 2 h of 25 μM phenol addition to the hepatocytes. The degree of cholesterogenesis reduction was similar for all phenol treatments (−25/30%), while fatty acid synthesis showed the following order of inhibition: hydroxytyrosol (−49%) = oleuropein (−48%) > tyrosol (−30%). A phenol-induced reduction of triglyceride synthesis was also detected. To clarify the lipid-lowering mechanism of these compounds, their influence on the activity of key enzymes of fatty acid biosynthesis (acetyl-CoA carboxylase and fatty acid synthase), triglyceride synthesis (diacylglycerol acyltransferase) and cholesterogenesis (3-hydroxy-3-methyl-glutaryl-CoA reductase) was investigated in situ by using digitonin-permeabilized hepatocytes. Acetyl-CoA carboxylase, diacylglycerol acyltransferase and 3-hydroxy-3-methyl-glutaryl-CoA reductase activities were reduced after 2 h of 25 μM phenol treatment. No change in fatty acid synthase activity was observed. Acetyl-CoA carboxylase inhibition (hydroxytyrosol, −41%, = oleuropein, −38%, > tyrosol, −17%) appears to be mediated by phosphorylation of AMP-activated protein kinase. These findings suggest that a decrease in hepatic lipid synthesis may represent a potential mechanism underlying the reported hypolipidemic effect of phenols of extra virgin olive oil. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
9. Hypothyroidism Reduces Tricarboxylate Carrier Activity and Expression in Rat Liver Mitochondria by Reducing Nuclear Transcription Rate and Splicing Efficiency.
- Author
-
Siculella, Luisa, Sabetta, Simona, Giudetti, Anna M., and Gnoni, Gabriele V.
- Subjects
- *
HYPOTHYROIDISM , *LABORATORY rats , *LIVER , *MITOCHONDRIA , *MESSENGER RNA - Abstract
The tricarboxylate carrier (TCC), also known as citrate carrier, is an integral protein of the mitochondrial inner membrane. It is an essential component of the shuttle system by which mitochondrial acetyl-CoA, primer for both fatty acid and cholesterol synthesis, is transported into the cytosol, where lipogenesis occurs. The effect of hypothyroidism on the activity and expression of the hepatic mitochondrial ICC was investigated in this study. TCC activity was significantly decreased in hypo-thyroid rats as compared with euthyroid animals. This hormone deficiency effect was due to a reduction in the amount of carrier protein, which resulted from a proportionate decrease of the specific mRNA. Hypothyroidism did not influence TCC mRNA stability. On the other hand, nuclear run-on assay revealed that the transcriptional rate of ICC mRNA decreased by ~40% in the nuclei from hypothyroid versus euthyroid rats. In addition, the ribonuclease protection assay showed that, in the nuclei of hypothyroid rats, the ratio of mature to precursor RNA decreased, indicating that the splicing of TCC RNA is affected. Furthermore, we found that the ratio of polyadenylated/unpolyadenylated ICC RNA as well as the length of the TCC RNA poly(A) tail were similar in both euthyroid and hypothyroid rats. Thus, the rate of formation of the TCC 3′-end is not altered in hypothyroidism. These results suggest that hypothyroidism affects TCC expression at both the transcriptional and post- transcriptional levels. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
10. Citrate carrier promoter is target of peroxisome proliferator-activated receptor alpha and gamma in hepatocytes and adipocytes
- Author
-
Damiano, Fabrizio, Gnoni, Gabriele V., and Siculella, Luisa
- Subjects
- *
CITRATES , *MITOCHONDRIAL membranes , *MEMBRANE proteins , *PROMOTERS (Genetics) , *PEROXISOME proliferator-activated receptors , *LIVER cells , *FAT cells - Abstract
Abstract: Citrate carrier (CiC), a mitochondrial inner membrane protein, is an essential component of the shuttle system which transports acetyl-CoA from mitochondria to the cytosol where lipogenesis occurs. CiC is regulated by SREBP-1, a transcription factor that controls the expression of several lipogenic genes. CiC is also implicated in cholesterol synthesis, glycolysis and gluconeogenesis, suggesting that besides SREBP-1 other transcription factors could modulate the expression of its gene. Here, we provide evidences demonstrating that CiC expression is regulated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma in hepatocytes and adipocytes, respectively. CiC expression increased in rat BRL-3A hepatocytes treated with WY-14,643, agonist of PPARα, and in murine 3T3-L1 adipocytes treated with rosiglitazone, agonist of PPARγ. The overexpression of PPARα/RXRα and PPARγ/RXRα heterodimer enhanced CiC promoter activity in BRL-3A and 3T3-L1, respectively. Luciferase reporter gene and gel mobility shift assays indicated that a functional peroxisome proliferator-activated receptor response element (PPRE), identified in the CiC promoter, conferred responsiveness to activation by PPARs. The binding of PPRE of CiC promoter by PPARα and PPARγin vivo was confirmed by ChIP assay in BRL-3A and 3T3-L1 cells, respectively. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
11. Hypothyroidism down-regulates mitochondrial citrate carrier activity and expression in rat liver
- Author
-
Giudetti, Anna M., Leo, Monica, Siculella, Luisa, and Gnoni, Gabriele V.
- Subjects
- *
FATTY acids , *HIGH performance liquid chromatography , *HYPOTHYROIDISM , *HYDROGEN-ion concentration - Abstract
Abstract: The effect of hypothyroidism on citrate carrier (CiC) activity has been investigated in rat-liver mitochondria. The rate of citrate transport was reduced by ∼50% in mitochondria from hypothyroid as compared with euthyroid rats. In parallel, a decrease in the rate of de novo fatty acid synthesis was observed in the cytosol of the former animals. Kinetic analysis of citrate transport revealed that only the V max was reduced by hypothyroidism, while K m was almost unaffected. Hypothyroidism increased the mitochondrial percentage of phosphatidylcholine while decreased that of phosphatidylethanolamine; an altered fatty acid pattern but no significant difference in the sum of saturated and unsaturated fatty acids as well as in the unsaturation index was observed. The CiC Arrhenius plot did not show appreciable difference between the two groups of rats. However, Western blot analysis associated with mRNA quantitation indicated that both protein level and mRNA accumulation of hepatic CiC were noticeably decreased in hypothyroid state. Therefore, a reduced content of the carrier protein can represent a plausible mechanism to explain the decline in the CiC activity observed in rat liver mitochondria of hypothyroid rats. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
12. Transcription of two sunflower (Helianthus annuus L.) mitochondrial tRNA genes having different genetic origins
- Author
-
Damiano, Fabrizio, Ceci, Luigi Ruggiero, Siculella, Luisa, and Gallerani, Raffaele
- Subjects
- *
GENETIC transcription , *TRANSFER RNA , *MITOCHONDRIAL DNA - Abstract
The divergent transcription of two tRNA genes encoded in sunflower mitochondrial DNA, proposed as genes of different genetic origin, has been studied in detail. The transcription initiation site (TIS) for both transcript precursors has been identified by hybridization with in vitro 32P-capped total RNAs and primer extension. The location of two TISs and the analysis of distribution of sequence elements (motifs) usually present in higher plant mitochondrial promoters led to the identification of two short regions (about 30–40 bp) which can be proposed as the promoters for the transcription of two genes. This conclusion is supported by the observation that within the short intergenic region included between the 5′ termini of two genes (1924 bp) the distribution of those specific motifs is unique around the TISs, although not identical for the two promoters. Based on specific experimental results the trnE promoter shows a higher efficiency in comparison with that of the trnH promoter. This result is in good agreement with its structure which strictly conforms to those described for mitochondrial genes of dicot plants. Instead the other promoter shows some divergences which could be responsible for its lower efficiency. The context in which trnH lies in the sunflower mitochondrial genome and other features described in the paper may suggest that, despite the high similarity with the chloroplast counterpart, the trnH gene could have a native origin. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
13. Exploring the significance of epicardial adipose tissue in aortic valve stenosis and left ventricular remodeling: Unveiling novel therapeutic and prognostic markers of disease.
- Author
-
Quarta, Stefano, Santarpino, Giuseppe, Carluccio, Maria Annunziata, Calabriso, Nadia, Maffia, Michele, Siculella, Luisa, Damiano, Fabrizio, Madonna, Rosalinda, and Massaro, Marika
- Subjects
- *
AORTIC stenosis , *AORTIC valve , *VENTRICULAR remodeling , *PROGNOSIS , *EPICARDIAL adipose tissue , *VENTRICULAR outflow obstruction - Abstract
Aortic stenosis (AS) is a dynamic degenerative process that shares many pathophysiological features with atherogenesis, from initial proinflammatory calcification and focal thickening of the valve leaflets to obstruction of left ventricular outflow due to superimposed of severe calcification and immobilization of the valve leaflets. As the prevalence increases with age, AS is expected to become one of the most common heart diseases worldwide. In both obese and nonobese patients, persistent thickening of epicardial adipose tissue (EAT) is associated with a shift in its normal metabolic functions toward a dysmetabolic and proatherogenic phenotype that may impair the physiology of adjacent coronary arteries and promote the occurrence of coronary atherosclerosis. In tight analogy with atherosclerosis, recent clinical evidence indicates that EAT may also exert a deleterious role in promoting AS and contributing to myocardial dysfunction, leading to increased health risk for elderly patients with AS and an economic burden on the health care system. This review discusses the clinical and pathologic evidence for the association between EAT and AS and concomitant left ventricular hypertrophy, and provides new insights for the future direction of AS diagnosis and treatment. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
14. Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an internal ribosome entry site in response to ER stress, serum deprivation or hypoxia mimetic CoCl2.
- Author
-
Damiano, Fabrizio, Testini, Mariangela, Tocci, Romina, Gnoni, Gabriele V., and Siculella, Luisa
- Subjects
- *
ACETYL-CoA carboxylase , *BIOSYNTHESIS , *MESSENGER RNA , *LIPID metabolism , *CANCER cells , *LIVER cancer , *CANCER treatment - Abstract
Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5′ untranslated region (5′ UTR) of the ACC1 mRNA. Transfection experiments with the ACC1 5′ UTR inserted in a dicistronic reporter vector show a remarkable increase in the downstream cistron translation, through a cap-independent mechanism. The endoplasmic reticulum (ER) stress condition and the related unfolded protein response (UPR), triggered by treatment with thapsigargin and tunicamycin, cause an increase of the cap-independent translation of ACC1 mRNA in HepG2 cells, despite the overall reduction in global protein synthesis. Other stress conditions, such as serum starvation and incubation with hypoxia mimetic agent CoCl 2 , up-regulate ACC1 expression in HepG2 cells at the translational level. Overall, these findings indicate that the presence of an IRES in the ACC1 5′ UTR allows ACC1 mRNA translation in conditions that are inhibitory to cap-dependent translation. A potential involvement of the cap-independent translation of ACC1 in several pathologies, such as obesity and cancer, has been discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
15. Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia.
- Author
-
Lunetti, Paola, Damiano, Fabrizio, De Benedetto, Giuseppe, Siculella, Luisa, Pennetta, Antonio, Muto, Luigina, Paradies, Eleonora, Thomas Marobbio, Carlo Marya, Dolce, Vincenza, and Capobianco, Loredana
- Subjects
- *
GLYCINE , *HEME , *ANEMIA , *PROTEIN synthesis , *COENZYME A , *AMINOLEVULINIC acid - Abstract
Heme is an essential molecule in many biological processes, such as transport and storage of oxygen and electron transfer as well as a structural component of hemoproteins. Defects of heme biosynthesis in developing erythroblasts have profound medical implications, as represented by sideroblastic anemia. The synthesis of heme requires the uptake of glycine into the mitochondrial matrix where glycine is condensed with succinyl coenzyme A to yield δ-aminolevulinic acid. Herein we describe the biochemical and molecular characterization of yeast Hem25p and human SLC25A38, providing evidence that they are mitochondrial carriers for glycine. In particular, the hem25Δ mutant manifests a defect in the biosynthesis of aminolevulinic acid and displays reduced levels of downstream heme and mitochondrial cytochromes. The observed defects are rescued by complementation with yeast HEM25 or human SLC25A38 genes. Our results identify new proteins in the heme biosynthetic pathway and demonstrate that Hem25p and its human orthologue SLC25A38 are the main mitochondrial glycine transporters required for heme synthesis, providing definitive evidence of their previously proposed glycine transport function. Furthermore, our work may suggest new therapeutic approaches for the treatment of congenital sideroblastic anemia. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
16. Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis.
- Author
-
Serviddio, Gaetano, Bellanti, Francesco, Stanca, Eleonora, Lunetti, Paola, Blonda, Maria, Tamborra, Rosanna, Siculella, Luisa, Vendemiale, Gianluigi, Capobianco, Loredana, and Giudetti, Anna Maria
- Subjects
- *
CIRRHOSIS of the liver , *PHYSIOLOGICAL effects of antioxidants , *MITOCHONDRIAL pathology , *ORIGIN of life , *LABORATORY rats , *LIVER cells - Abstract
The accumulation of toxic hydrophobic bile acids in hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In this work we report that changes observed in the expression of the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase were associated with a decrease in the activity of citrate carrier (CIC), a protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of the phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and anti-inflammatory properties, prevented mitochondrial reactive oxygen species (ROS) production, cardiolipin oxidation, and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusion, we demonstrate that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
17. 3,5-Diiodo-l-thyronine induces SREBP-1 proteolytic cleavage block and apoptosis in human hepatoma (Hepg2) cells.
- Author
-
Rochira, Alessio, Damiano, Fabrizio, Marsigliante, Santo, Gnoni, Gabriele V., and Siculella, Luisa
- Subjects
- *
STEROL regulatory element-binding proteins , *THYRONINES , *THYROID hormones , *APOPTOSIS , *HEPATOCELLULAR carcinoma , *CELL metabolism , *TRANSCRIPTION factors - Abstract
Abstract: Thyroid hormone 3,5,3′-triiodo-l-thyronine (T3) is known to affect cell metabolism through both the genomic and non-genomic actions. Recently, we demonstrated in HepG2 cells that T3 controls the expression of SREBP-1, a transcription factor involved in the regulation of lipogenic genes. This occurs by activation of a cap-independent translation mechanism of its mRNA. Such a process is dependent on non-genomic activation of both MAPK/ERK and PI3K/Akt pathways. The physiological role of 3,5-diiodo-l-thyronine (T2), previously considered only as a T3 catabolite, is of growing interest. Evidences have been reported that T2 rapidly affects some metabolic pathways through non-genomic mechanisms. Here, we show that T2, unlike T3, determines the block of proteolytic cleavage of SREBP-1 in HepG2 cells, without affecting its expression at the transcriptional or translational level. Consequently, Fatty Acid Synthase expression is reduced. T2 effects depend on the concurrent activation of MAPKs ERK and p38, of Akt and PKC-δ pathways. Upon the activation of these signals, apoptosis of HepG2 cells seems to occur, starting at 12h of T2 treatment. PKC-δ appears to act as a switch between p38 activation and Akt suppression, suggesting that this PKC may function as a controller in the balance of pro-apoptotic (p38) and anti-apoptotic (Akt) signals in HepG2 cells. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
18. Down-regulation of LPCAT expression increases platelet-activating factor level in cirrhotic rat liver: Potential antiinflammatory effect of silybin.
- Author
-
Stanca, Eleonora, Serviddio, Gaetano, Bellanti, Francesco, Vendemiale, Gianluigi, Siculella, Luisa, and Giudetti, Anna Maria
- Subjects
- *
GENETIC regulation , *GENE expression , *PLATELET activating factor , *CIRRHOSIS of the liver , *LABORATORY rats , *ANTI-inflammatory agents , *SILYMARIN - Abstract
Abstract: Cholestasis is one of the major causes of liver diseases. A chronic accumulation of toxic bile acids in the liver, which occurs in this condition, can induce fibrosis and cirrhosis. Inflammation is a fundamental component of acute and chronic cholestatic liver injury. Platelet-activating factor (PAF) is a proinflammatory lipid which may be generated by two independent pathways called the de novo and remodeling pathway being the last responsible for the synthesis of PAF during inflammation. In recent years a key role in PAF remodeling has been attributed to lysophosphatidylcholine acyltransferase (LPCAT) enzymes. Although the knowledge on their characteristic is growing, the exact mechanism of LPCAT in pathological conditions remains still unknown. Here, we reported that the level of lyso-PAF and PAF significantly increased in the liver of cirrhotic vs. control rats together with a significant decrease in both mRNA abundance and protein level of both LPCAT1 and LPCAT2. Acyltransferase activities of both LPCAT1 and LPCAT2 were parallel decreased in the liver of cirrhotic animals. Interestingly, treatment with silybin strongly decreased the level of both pro-inflammatory lipids and restored the activity and expression of both LPCAT1 and LPCAT2 of cirrhotic liver. Silybin effect was specific for LPCAT1 and LPCAT2 since it did not affect LPCAT3 mRNA abundance of cirrhotic liver. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
19. Low level of hydrogen peroxide induces lipid synthesis in BRL-3A cells through a CAP-independent SREBP-1a activation.
- Author
-
Giudetti, Anna Maria, Damiano, Fabrizio, Gnoni, Gabriele Vincenzo, and Siculella, Luisa
- Subjects
- *
LIPID synthesis , *PHYSIOLOGICAL effects of hydrogen peroxide , *TRANSLATION initiation factors (Biochemistry) , *STEROL regulatory element-binding proteins , *LIPID metabolism , *OXIDATIVE stress , *LACTATE dehydrogenase - Abstract
Abstract: Although H2O2 is traditionally known to have cytotoxic effects, recent studies argue about its regulatory role on lipid metabolism. However, the mechanism underlying the induction of lipid biosynthesis by oxidative stress still remains unknown. To shed light on this aspect we investigated the H2O2-induced lipogenesis in rat liver BRL-3A cells. We found that a short-term exposition of cells to 35μM H2O2 didn’t cause any significant sign of cell damage measured by following diene formation and lactate dehydrogenase release from cells. However, in this stressful condition, a significant increase of [1-14C]acetate incorporation into fatty acids and cholesterol, associated to an increase in the activity and expression of key enzymes of fatty acid and cholesterol synthesis, were measured. mRNA and protein contents of the transcription factors SREBP-1 and SREBP-2, involved in the activation of lipid synthesis, increased as well. The analysis of molecular mechanism of SREBP-1 activation revealed, in treated compared to control cells, a higher SREBP-1a mRNA translation involving an internal ribosome entry side (IRES), present in the leader region of its mRNA. Longer exposition to the pro-oxidant induced a progressive loss of cell viability together with an increase of cell triacylglycerol content. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
20. Dietary fat types differently modulate the activity and expression of mitochondrial carnitine/acylcarnitine translocase in rat liver
- Author
-
Priore, Paola, Stanca, Eleonora, Gnoni, Gabriele Vincenzo, and Siculella, Luisa
- Subjects
- *
GENE expression , *MITOCHONDRIA , *FAT , *CARNITINE palmitoyltransferase , *CARNITINE , *MEMBRANE proteins , *FATTY acids , *LABORATORY rats - Abstract
Abstract: The carnitine/acylcarnitine translocase (CACT), an integral protein of the mitochondrial inner membrane, belongs to the carnitine-dependent system of fatty acid transport into mitochondria, where beta-oxidation occurs. CACT exchanges cytosolic acylcarnitine or free carnitine for carnitine in the mitochondrial matrix. The object of this study was to investigate in rat liver the effect, if any, of diets enriched with saturated fatty acids (beef tallow, BT, the control), n−3 polyunsaturated fatty acids (PUFA) (fish oil, FO), n−6 PUFA (safflower oil, SO), and mono-unsaturated fatty acids (MUFA) (olive oil, OO) on the activity and expression of CACT. Translocase exchange rates increased, in parallel with CACT mRNA abundance, upon FO-feeding, whereas OO-dietary treatment induced a decrease in both CACT activity and expression. No changes were observed upon SO-feeding. Nuclear run-on assay revealed that FO-treatment increased the transcriptional rate of CACT mRNA. On the other hand, only in the nuclei of hepatocytes from OO-fed rats splicing of the last intron of CACT pre-mRNA and the rate of formation of the 3′-end were affected. Overall, these findings suggest that compared to the BT‐enriched diet, the SO-enriched diet did not influence CACT activity and expression, whereas FO- and OO-feeding alters CACT activity in an opposite fashion, i.e. modulating its expression at transcriptional and post-transcriptional levels, respectively. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
21. Streptozotocin-induced diabetes affects in rat liver citrate carrier gene expression by transcriptional and posttranscriptional mechanisms
- Author
-
Damiano, Fabrizio, Mercuri, Elisa, Stanca, Eleonora, Gnoni, Gabriele Vincenzo, and Siculella, Luisa
- Subjects
- *
ANIMAL models of diabetes , *STREPTOZOTOCIN , *LABORATORY rats , *GENE expression , *CITRATES , *GENETIC transcription , *ACETYLCOENZYME A , *ADENINE nucleotides - Abstract
Abstract: Citrate carrier (CiC), also known as tricarboxylate carrier, is an integral protein of the mitochondrial inner membrane. It is an essential component of the shuttle system by which mitochondrial acetyl-CoA, primer for both fatty acid and cholesterol synthesis, is transported into the cytosol, where lipogenesis occurs. Here, we report the effect of streptozotocin-induced diabetes on the activity and expression of CiC in rat liver mitochondria. A significant reduction of CiC activity and a parallel decline in the abundance of CiC mRNA were found in liver from diabetic rats. Diabetes did not influence CiC mRNA stability, whereas nuclear run-on assay revealed that the transcriptional rate of CiC mRNA decreased, when compared to control, in the nuclei from diabetic rats. The ratio of mature to precursor CiC RNA decreased in diabetic animals, indicating that the splicing of CiC RNA was also affected. The 3′-end processing rate of CiC mRNA was not altered in diabetes. These results suggest that diabetes affects CiC expression at both transcriptional and posttranscriptional levels. In addition, by in vitro transfection experiments in rat hepatocytes cultured in the absence of insulin, a reduction of CiC promoter activity was observed, and this was ascribed to a decreased expression of sterol regulatory element-binding protein-1 transcriptional factor. Furthermore, the binding of sterol regulatory element-binding protein-1 to the CiC promoter was reduced in STZ-diabetic rats with respect to control ones, and it was restored to the control values after insulin treatment. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
22. 3,5-diiodo-L-thyronine upregulates rat-liver mitochondrial FoF1-ATP synthase by GA-binding protein/nuclear respiratory factor-2
- Author
-
Mangiullo, Roberto, Gnoni, Antonio, Damiano, Fabrizio, Siculella, Luisa, Zanotti, Franco, Papa, Sergio, and Gnoni, Gabriele V.
- Subjects
- *
THYRONINES , *LIVER physiology , *LABORATORY rats , *ADENOSINE triphosphatase , *PROTEIN binding , *BIOENERGETICS , *MITOCHONDRIAL membranes , *SOMATOTROPIN - Abstract
Abstract: Besides triiodothyronine (T3), 3,5-diiodo-L-thyronine (T2) has been reported to affect mitochondrial bioenergetic parameters. T2 effects have been considered as independent of protein synthesis. Here, we investigated the effect of in vivo chronic T2 administration to hypothyroid rats on liver mitochondrial FoF1-ATP synthase activity and expression. T2 increased state 4 and state 3 oxygen consumption and raised ATP synthesis and hydrolysis, which were reduced in hypothyroid rats. Immunoblotting analysis showed that T2 up-regulated the expression of several subunits (α, β, FoI-PVP and OSCP) of the ATP synthase. The observed increase of β-subunit mRNA accumulation suggested a T2-mediated nuclear effect. Then, the molecular basis underlying T2 effects was investigated. Our results support the notion that the β-subunit of ATP synthase is indirectly regulated by T2 through, at least in part, the activation of the transcription factor GA-binding protein/nuclear respiratory factor-2. These findings provide new insights into the T2 role on bioenergetic mechanisms. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
23. Quercetin inhibition of SREBPs and ChREBP expression results in reduced cholesterol and fatty acid synthesis in C6 glioma cells.
- Author
-
Damiano, Fabrizio, Giannotti, Laura, Gnoni, Gabriele V., Siculella, Luisa, and Gnoni, Antonio
- Subjects
- *
QUERCETIN , *FATTY acids , *CHOLESTEROL , *ACETYL-CoA carboxylase , *LIPID synthesis , *TRANSCRIPTION factors - Abstract
• Quercetin rapidly inhibits cholesterol and fatty acid synthesis in C6 glioma cells. • Quercetin reduces the activity of ACC1 and HMGCR. • Quercetin acts at transcriptional level by decreasing expression of SREBPs and ChREBP. Quercetin (Que), a widely distributed flavonoid in the human diet, exerts neuroprotective action because of its property to antagonize oxidative stress. Here, we investigated the effects of Que on lipid synthesis in C6 glioma cells. A rapid Que-induced inhibition of cholesterol and, to a lesser extent, of fatty acid synthesis from [1-14C]acetate was observed. The maximum decrease was detected at the level of palmitate, the end product of de novo fatty acid synthesis. The effect of Que on the enzyme activities of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS), the two enzymes of this pathway, was investigated directly in situ in permeabilized C6 cells. An inhibitory effect on ACC1 was observed after 4 h of 25 μM Que treatment, while FAS activity was not affected. A reduction of polar lipid biosynthesis was also detected. A remarkable decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) activity, regulatory enzyme of cholesterol synthesis, was evidenced. Expression studies demonstrated that Que acts at transcriptional level, by reducing the mRNA abundance and protein amount of ACC1 and HMGCR. Deepening the molecular mechanism, we found that Que decreased the expression of SREBP-1 and SREBP-2, transcriptional factors representing the main regulators of de novo fatty acid and cholesterol synthesis, respectively. Que also reduced the nuclear content of ChREBP, a glucose-induced transcription factor involved in the regulation of lipogenic genes. Our results represent the first evidence that a direct and rapid downregulatory effect of Que on cholesterol and de novo fatty acid synthesis is elicited in C6 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
24. 3,5-diiodo-L-thyronine upregulates rat-liver mitochondrial FoF1-ATP synthase by GA-binding protein/nuclear respiratory factor-2
- Author
-
Roberto Mangiullo, Luisa Siculella, Sergio Papa, Franco Zanotti, Gabriele V. Gnoni, Fabrizio Damiano, Antonio Gnoni, Mangiullo, Roberto, Gnoni, A, Damiano, Fabrizio, Siculella, Luisa, Zanotti, F, Papa, S, and Gnoni, Gabriele Vincenzo
- Subjects
Male ,Chromatin Immunoprecipitation ,Bioenergetics ,Diiodothyronines ,Immunoblotting ,Biophysics ,Mitochondria, Liver ,Oxidative phosphorylation ,Biology ,Biochemistry ,chemistry.chemical_compound ,Oxygen Consumption ,Hypothyroidism ,Rat-liver mitochondria ,Protein biosynthesis ,Animals ,RNA, Messenger ,Rats, Wistar ,Transcription factor ,Membrane Potential, Mitochondrial ,Messenger RNA ,Triiodothyronine ,ATP synthase ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Biology ,Mitochondrial Proton-Translocating ATPases ,GA-Binding Protein Transcription Factor ,FoF1-ATP synthase ,Rats ,chemistry ,Nuclear respiratory factor-2 ,Thyronine ,biology.protein ,5-diiodothyronine ,3,5-diiodothyronine - Abstract
Besides triiodothyronine (T3), 3,5-diiodo-L-thyronine (T2) has been reported to affect mitochondrial bioenergetic parameters. T2 effects have been considered as independent of protein synthesis. Here, we investigated the effect of in vivo chronic T2 administration to hypothyroid rats on liver mitochondrial F(o)F(1)-ATP synthase activity and expression. T2 increased state 4 and state 3 oxygen consumption and raised ATP synthesis and hydrolysis, which were reduced in hypothyroid rats. Immunoblotting analysis showed that T2 up-regulated the expression of several subunits (alpha, beta, F(o)I-PVP and OSCP) of the ATP synthase. The observed increase of beta-subunit mRNA accumulation suggested a T2-mediated nuclear effect. Then, the molecular basis underlying T2 effects was investigated. Our results support the notion that the beta-subunit of ATP synthase is indirectly regulated by T2 through, at least in part, the activation of the transcription factor GA-binding protein/nuclear respiratory factor-2. These findings provide new insights into the T2 role on bioenergetic mechanisms.
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.