7 results on '"E. Diane Wallace"'
Search Results
2. Obesity reprograms the pulmonary polyunsaturated fatty acid-derived lipidome, transcriptome, and gene-oxylipin networks
- Author
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Rafia Virk, Nicole Buddenbaum, Abrar Al-Shaer, Michael Armstrong, Jonathan Manke, Nichole Reisdorph, Selin Sergin, Jenifer I. Fenton, E. Diane Wallace, Brandie M. Ehrmann, Hannah B. Lovins, Kymberly M. Gowdy, M Ryan Smith, Gregory J. Smith, Samir N.P. Kelada, and Saame Raza Shaikh
- Subjects
arachidonic acid ,high-fat diet ,oxylipins ,inflammation ,nutrition ,omega-3 fatty acids ,Biochemistry ,QD415-436 - Abstract
Obesity exacerbates inflammation upon lung injury; however, the mechanisms by which obesity primes pulmonary dysregulation prior to external injury are not well studied. Herein, we tested the hypothesis that obesity dysregulates pulmonary PUFA metabolism that is central to inflammation initiation and resolution. We first show that a high-fat diet (HFD) administered to C57BL/6J mice increased the relative abundance of pulmonary PUFA-containing triglycerides and the concentration of PUFA-derived oxylipins (particularly prostaglandins and hydroxyeicosatetraenoic acids), independent of an increase in total pulmonary PUFAs, prior to onset of pulmonary inflammation. Experiments with a genetic model of obesity (ob/ob) generally recapitulated the effects of the HFD on the pulmonary oxylipin signature. Subsequent pulmonary next-generation RNA sequencing identified complex and unique transcriptional regulation with the HFD. We found the HFD increased pathways related to glycerophospholipid metabolism and immunity, including a unique elevation in B cell differentiation and signaling. Furthermore, we conducted computational integration of lipidomic with transcriptomic data. These analyses identified novel HFD-driven networks between glycerophospholipid metabolism and B cell receptor signaling with specific PUFA-derived pulmonary oxylipins. Finally, we confirmed the hypothesis by demonstrating that the concentration of pulmonary oxylipins, in addition to inflammatory markers, were generally increased in mice consuming a HFD upon ozone-induced acute lung injury. Collectively, these data show that a HFD dysregulates pulmonary PUFA metabolism prior to external lung injury, which may be a mechanism by which obesity primes the lungs to respond poorly to infectious and/or inflammatory challenges.
- Published
- 2022
- Full Text
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3. APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size
- Author
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Ian A. Windham, Joey V. Ragusa, E. Diane Wallace, Colby H. Wagner, Kristen K. White, and Sarah Cohen
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Article - Abstract
TheE4variant ofAPOEstrongly predisposes individuals to late-onset Alzheimer’s disease. We demonstrate that in response to neutral lipid synthesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the ER lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts.APOEknockdown promotes fewer, larger LDs containing more unsaturated triglyceride. This LD size distribution phenotype was rescued by chimeric APOE that targets only LDs. APOE4-expressing astrocytes also form a small number of large LDs enriched in unsaturated triglyceride. Additionally, the larger LDs inAPOE4cells exhibit impaired turnover and increased sensitivity to lipid peroxidation. Our data indicate that APOE plays a previously unrecognized role as an LD surface protein that regulates LD size and composition.APOE4is a toxic gain of function variant that causes aberrant LD composition and morphology. We propose thatAPOE4astrocytes with large, unsaturated LDs are sensitized to lipid peroxidation or lipotoxicity, which could contribute to Alzheimer’s disease risk.SummaryWindhamet al. discover that APOE in astrocytes can traffic to lipid droplets (LDs), where it modulates LD composition and size. Astrocytes expressing the Alzheimer’s risk variant APOE4 form large LDs with impaired turnover and increased peroxidation sensitivity.
- Published
- 2023
4. Glycerolipid defects in skeletal muscle contribute to rhabdomyolysis in Tango2 deficiency
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Jennifer G Casey, Euri S Kim, Brian S Tao, Arian Mansur, E. Diane Wallace, and Vandana A Gupta
- Abstract
Rhabdomyolysis is a clinical emergency characterized by severe muscle damage resulting in the release of intracellular muscle components leading to myoglobinuria and in severe cases, acute kidney failure. Rhabdomyolysis is caused by genetic factors that are linked to increased disease susceptibility in response to extrinsic triggers. Recessive mutations inTANGO2result in episodic rhabdomyolysis, metabolic crises, encephalopathy and cardiac arrhythmia, the underlying mechanism contributing to disease onset in response to specific triggers remains unclear. To address these challenges, we created a zebrafish model of Tango2 deficiency. Here we show that loss of Tango2 in zebrafish results in growth defects, early lethality and increased susceptibility of muscle defects similar toTANGO2patients. Detailed analyses of skeletal muscle revealed defects in the sarcoplasmic reticulum and mitochondria at the onset of disease development. The sarcoplasmic reticulum (SR) constitutes the primary lipid biosynthesis site and regulates calcium handling in skeletal muscle to control excitation-contraction coupling. Tango2 deficient SR exhibits increased sensitivity to calcium release that was partly restored by inhibition of Ryr1-mediated Ca2+release in skeletal muscle. Using lipidomics, we identified alterations in the glycerolipid state oftango2mutants which is critical for membrane stability and energy balance. Therefore, these studies provide insight into key disease processes in Tango2 deficiency and increased our understanding of how specific defects can predispose to environmental triggers in TANGO2-related disorders.
- Published
- 2022
5. Scavenger receptor BI attenuates oxidized phospholipid-induced pulmonary inflammation
- Author
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Katelyn Dunigan-Russell, Michael J. Yaeger, Myles X. Hodge, Brita Kilburg-Basnyat, Sky W. Reece, Anastasiya Birukova, Marissa A. Guttenberg, Caymen Novak, Sangwoon Chung, Brandie Michelle Ehrmann, E. Diane Wallace, Debra Tokarz, Nairrita Majumder, Li Xia, John W. Christman, Jonathan Shannahan, Megan N. Ballinger, Salik Hussain, Saame Raza Shaikh, Robert M. Tighe, and Kymberly M. Gowdy
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Pharmacology ,Toxicology - Published
- 2023
6. The Chemistry of Kratom [Mitragyna speciosa]: Updated Characterization Data and Methods to Elucidate Indole and Oxindole Alkaloids
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Mario Augustinović, Nadja B. Cech, Daniel A. Todd, Laura Flores-Bocanegra, Nicholas H. Oberlies, Shabnam Hematian, E. Diane Wallace, Huzefa A. Raja, Joshua J. Kellogg, and Tyler N. Graf
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Stereochemistry ,Mitragyna speciosa ,Pharmaceutical Science ,01 natural sciences ,Article ,Indole Alkaloids ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Discovery ,Oxindole ,Pharmacology ,Indole test ,Molecular Structure ,biology ,Indole alkaloid ,Mitragyna ,010405 organic chemistry ,Chemistry ,Spectrum Analysis ,Organic Chemistry ,Absolute configuration ,Stereoisomerism ,Carbon-13 NMR ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Mitragynine ,Molecular Medicine ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Two separate commercial products of kratom [Mitragyna speciosa (Korth.) Havil. Rubiaceae] were used to generate reference standards of its indole and oxindole alkaloids. While kratom has been studied for over a century, the characterization data in the literature for many of the alkaloids are either incomplete or inconsistent with modern standards. As such, full (1)H and (13)C NMR spectra, along with HRESIMS and ECD data, are reported for alkaloids 1-19. Of these, four new alkaloids (7, 11, 17, and 18) were characterized using 2D NMR data, and the absolute configurations of 7, 17, and 18 were established by comparison of experimental and calculated ECD spectra. The absolute configuration for the N(4)-oxide (11) was established by comparison of NMR and ECD spectra of its reduced product with those for compound 7. In total, 19 alkaloids were characterized, including: the indole alkaloid mitragynine (1) and its diastereoisomers speciociliatine (2), speciogynine (3) and mitraciliatine (4); the indole alkaloid paynantheine (5) and its diastereoisomers isopaynantheine (6) and epiallo-isopaynantheine (7); the N(4)-oxides mitragynine-N(4)-oxide (8), speciociliatine-N(4)-oxide (9), isopaynantheine-N(4)-oxide (10), and epiallo-isopaynantheine-N(4)-oxide (11); the 9-hydroxylated oxindole alkaloids speciofoline (12), isorotundifoleine (13) and isospeciofoleine (14); and the 9-unsubstituted oxindoles corynoxine A (15), corynoxine B (16), 3-epirhynchophylline (17), 3-epicorynoxine B (18), and corynoxeine (19). With the ability to analyze the spectroscopic data of all of these compounds concomitantly, a decision tree was developed to differentiate these kratom alkaloids based on a few key chemical shifts in the (1)H and/or (13)C NMR spectra.
- Published
- 2020
7. Identification of Adulteration in Botanical Samples with Untargeted Metabolomics
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James M. Harnly, E. Diane Wallace, Joshua J. Kellogg, Nadja B. Cech, and Daniel A. Todd
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Adulterant ,Hydrastis ,Principal Component Analysis ,Training set ,Chromatography ,Composite score ,Palmatine ,Biology ,Coptis chinensis ,biology.organism_classification ,Biochemistry ,Article ,Mass Spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,Untargeted metabolomics ,Metabolomics ,chemistry ,Dietary Supplements ,Identification (biology) ,Drug Contamination ,Chromatography, High Pressure Liquid ,Coptis - Abstract
Adulteration remains an issue in the dietary supplement industry, including botanical supplements. While it is common to employ a targeted analysis to detect known adulterants, this is difficult when little is known about the sample set. With this study, untargeted metabolomics using liquid chromatography coupled to ultraviolet-visible spectroscopy (LC-UV) or high-resolution mass spectrometry (LC-MS) was employed to detect adulteration in botanical dietary supplements. A training set was prepared by combining Hydrastis canadensis L. with a known adulterant, Coptis chinensis Franch., in ratios ranging from 5 to 95% adulteration. The metabolomics datasets were analyzed using both unsupervised (principal component analysis and composite score) and supervised (SIMCA) techniques. Palmatine, a known H. canadensis metabolite, was quantified as a targeted analysis comparison. While the targeted analysis was the most sensitive method tested in detecting adulteration, statistical analyses of the untargeted metabolomics datasets detected adulteration of the goldenseal samples, with SIMCA providing the greatest discriminating potential. Graphical abstract.
- Published
- 2020
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