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Branka Sosic-jurjevic - One of the best experts on this subject based on the ideXlab platform.
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Citrus flavanones naringenin and hesperetin improve antioxidant status and Membrane lipid compositions in the liver of old-aged Wistar rats
Experimental Gerontology, 2016Co-Authors: Marko Miler, Jasmina Zivanovic, Vladimir Ajdzanovic, Zorana Orescanin-dusic, Dragan Milenkovic, Aleksandra Konic-ristic, Dusko Blagojevic, Verica Milosevic, Branka Sosic-jurjevicAbstract:This study aimed to investigate effects of citrus flavanones naringenin (NAR) and hesperetin (HES) on liver antioxidant status and Membrane Phospholipid composition in 24-month-old rats. NAR and HES (15 mg/kg) were administrated orally to male Wistar rats, once per day, for 4 weeks. Control group received either vehicle (sunflower oil) or remained intact. The results showed decreased (p < 0.05) activity of antioxidant enzymes (AOE), specifically catalase (CAT), superoxide dismutase (SOD) 1 and glutathione reductase (GR) in the liver of intact control old-aged rats in comparison to young intact controls. Flavanone administration to old-aged males increased (p < 0.05) examined AOE activities in comparison to vehicle-administered animals. Namely, NAR was more potent in comparison to HES regarding the increase (p < 0.05) in activities of examined antioxidant enzymes (SOD 1 and 2, glutathione peroxidase-GPx and GR) and the liver glutathione (GSH), while HES elevated (p < 0.05) only activity of CAT and GR. Both flavanones significantly decreased (p < 0.05) TBARS and improved (p < 0.05) Membrane Phospholipid composition in favor of n-3 PUFA and n-6/n-3 PUFA ratio. Both flavanones did not affect liver histology and reduced (p < 0.05) alanine aminotransferase and aspartate aminotransferase levels in serum. The results of this study indicate beneficial potential of citrus flavanones in the old-aged rat liver
William Dowhan - One of the best experts on this subject based on the ideXlab platform.
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impact of Membrane Phospholipid alterations in escherichia coli on cellular function and bacterial stress adaptation
Journal of Bacteriology, 2017Co-Authors: Veronica W Rowlett, Venkata K P S Mallampalli, Anja Karlstaedt, William Dowhan, Heinrich Taegtmeyer, William Margolin, Heidi VitracAbstract:Bacteria have evolved multiple strategies to sense and rapidly adapt to challenging and ever-changing environmental conditions. The ability to alter Membrane lipid composition, a key component of the cellular envelope, is crucial for bacterial survival and adaptation in response to environmental stress. However, the precise roles played by Membrane Phospholipids in bacterial physiology and stress adaptation are not fully elucidated. The goal of this study was to define the role of Membrane Phospholipids in adaptation to stress and maintenance of bacterial cell fitness. By using genetically modified strains in which the Membrane Phospholipid composition can be systematically manipulated, we show that alterations in major Escherichia coli Phospholipids transform these cells globally. We found that alterations in Phospholipids impair the cellular envelope structure and function, the ability to form biofilms, and bacterial fitness and cause Phospholipid-dependent susceptibility to environmental stresses. This study provides an unprecedented view of the structural, signaling, and metabolic pathways in which bacterial Phospholipids participate, allowing the design of new approaches in the investigation of lipid-dependent processes involved in bacterial physiology and adaptation.IMPORTANCE In order to cope with and adapt to a wide range of environmental conditions, bacteria have to sense and quickly respond to fluctuating conditions. In this study, we investigated the effects of systematic and controlled alterations in bacterial Phospholipids on cell shape, physiology, and stress adaptation. We provide new evidence that alterations of specific Phospholipids in Escherichia coli have detrimental effects on cellular shape, envelope integrity, and cell physiology that impair biofilm formation, cellular envelope remodeling, and adaptability to environmental stresses. These findings hold promise for future antibacterial therapies that target bacterial lipid biosynthesis.
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daptomycin resistance in enterococci is associated with distinct alterations of cell Membrane Phospholipid content
PLOS ONE, 2012Co-Authors: Nagendra N Mishra, William Dowhan, Arnold S Bayer, Truc T Tran, Yousif Shamoo, Eugenia Mileykovskaya, Ziqiang Guan, Cesar A AriasAbstract:Background: The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell Membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope homeostasis and Phospholipid metabolism. Here we characterized changes in CM Phospholipid profiles associated with development of DAP resistance in clinical enterococcal strains. Methodology: Using two clinical strain-pairs of DAP-susceptible and DAP-resistant E. faecalis (S613 vs. R712) and E. faecium (S447 vs. R446) recovered before and after DAP therapy, we compared four distinct CM profiles: Phospholipid content, fatty acid composition, Membrane fluidity and capacity to be permeabilized and/or depolarized by DAP. Additionally, we characterized the cell envelope of the E. faecium strain-pair by transmission electron microscopy and determined the relative cell surface charge of both strain-pairs. Principal Findings: Both E. faecalis and E. faecium mainly contained four major CM PLs: phosphatidylglycerol (PG), cardiolipin, lysyl-phosphatidylglycerol (L-PG) and glycerolphospho-diglycodiacylglycerol (GP-DGDAG). In addition, E. faecalis CMs (but not E. faecium) also contained: i ) phosphatidic acid; and ii ) two other unknown species of amino-containing PLs. Development of DAP resistance in both enterococcal species was associated with a significant decrease in CM fluidity and PG content, with a concomitant increase in GP-DGDAG. The strain-pairs did not differ in their outer CM translocation (flipping) of amino-containing PLs. Fatty acid content did not change in the E. faecalis strain-pair, whereas a significant decrease in unsaturated fatty acids was observed in the DAP-resistant E. faecium isolate R446 (vs S447). Resistance to DAP in E. faecium was associated with distinct structural alterations of the cell envelope and cell wall thickening, as well as a decreased ability of DAP to depolarize and permeabilize the CM. Conclusion: Distinct alterations in PL content and fatty acid composition are associated with development of enterococcal DAP resistance.
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molecular basis for Membrane Phospholipid diversity why are there so many lipids
Annual Review of Biochemistry, 1997Co-Authors: William DowhanAbstract:Phospholipids play multiple roles in cells by establishing the permeability barrier for cells and cell organelles, by providing the matrix for the assembly and function of a wide variety of catalytic processes, by acting as donors in the synthesis of macromolecules, and by actively influencing the functional properties of Membrane-associated processes. The function, at the molecular level, of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin in specific cellular processes is reviewed, with a focus on the results of combined molecular genetic and biochemical studies in Escherichia coli. These results are compared with primarily biochemical data supporting similar functions for these Phospholipids in eukaryotic organisms. The wide range of processes in which specific involvement of Phospholipids has been documented explains the need for diversity in Phospholipid structure and why there are so many Membrane lipids.
Gil-soo Han - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidate phosphatase regulates Membrane Phospholipid synthesis via phosphatidylserine synthase.
Advances in biological regulation, 2017Co-Authors: George M. Carman, Gil-soo HanAbstract:Abstract The yeast Saccharomyces cerevisiae serves as a model eukaryote to elucidate the regulation of lipid metabolism. In exponentially growing yeast, a diverse set of Membrane lipids are synthesized from the precursor phosphatidate via the liponucleotide intermediate CDP-diacylglycerol. As cells exhaust nutrients and progress into the stationary phase, phosphatidate is channeled via diacylglycerol to the synthesis of triacylglycerol. The CHO1 -encoded phosphatidylserine synthase, which catalyzes the committed step in Membrane Phospholipid synthesis via CDP-diacylglycerol, and the PAH1 -encoded phosphatidate phosphatase, which catalyzes the committed step in triacylglycerol synthesis are regulated throughout cell growth by genetic and biochemical mechanisms to control the balanced synthesis of Membrane Phospholipids and triacylglycerol. The loss of phosphatidate phosphatase activity (e.g., pah1 Δ mutation) increases the level of phosphatidate and its conversion to Membrane Phospholipids by inducing Cho1 expression and phosphatidylserine synthase activity. The regulation of the CHO1 expression is mediated through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2–Ino4/Opi1) regulatory circuit. Consequently, phosphatidate phosphatase activity regulates Phospholipid synthesis through the transcriptional regulation of the phosphatidylserine synthase enzyme.
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Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for Membrane Phospholipid synthesis
The Journal of biological chemistry, 2017Co-Authors: Gil-soo Han, George M. CarmanAbstract:Abstract The PAH1-encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae, exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of Membrane Phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in Phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1-encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major Phospholipids via the CDP–diacylglycerol pathway. The lack of PAP in the pah1Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1. Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1Δ mutant is induced through the inositol-sensitive upstream activation sequence (UASINO), a cis-acting element for the phosphatidate-controlled Henry (Ino2–Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UASINO mutation suppressed pah1Δ effects on lipid synthesis, nuclear/endoplasmic reticulum Membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1-encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for Membrane Phospholipid synthesis.
Ashis K. Mukherjee - One of the best experts on this subject based on the ideXlab platform.
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Differential hydrolysis of erythrocyte and mitochondrial Membrane Phospholipids by two phospholipase A2 isoenzymes (NK-PLA2-I and NK-PLA2-II) from the venom of the Indian monocled cobra Naja kaouthia.
Archives of Biochemistry and Biophysics, 2004Co-Authors: Robin Doley, Glenn F. King, Ashis K. MukherjeeAbstract:We previously demonstrated that venom from the Indian monocled cobra Naja kaouthia is a rich source of phospholipase A2 enzymes, and we purified and characterized a major PLA2 isoenzyme (NK-PLA2-I) from N. kaouthia venom. In the present study, we report the purification and biochemical characterization of a second PLA2 isoenzyme (NK-PLA2-II) from the same venom. A comparison of the Membrane Phospholipid hydrolysis patterns by these two PLA2s has revealed that they cause significantly more damage to mitochondrial Membranes (NK-PLA2-I > NK-PLA2-II) as compared to erythrocyte Membranes due to more efficient binding of the enzymes to mitochondrial Membranes. Fatty acid release patterns by these PLA2s from the Membrane Phospholipid PC-pools indicate that NK-PLA2-I does not discriminate between saturated and unsaturated fatty acids whereas NK-PLA2-II shows a preference for unsaturated fatty acids during the initial phase of attack. The current investigation provides new insight into the molecular arrangement of NK-PLA2-sensitive domains in erythrocyte and mitochondrial Membranes and highlights the contribution of polar, but uncharged, amino acids such as serine and cysteine in NK-PLA2 induced Membrane damage.
George M. Carman - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidate phosphatase regulates Membrane Phospholipid synthesis via phosphatidylserine synthase.
Advances in biological regulation, 2017Co-Authors: George M. Carman, Gil-soo HanAbstract:Abstract The yeast Saccharomyces cerevisiae serves as a model eukaryote to elucidate the regulation of lipid metabolism. In exponentially growing yeast, a diverse set of Membrane lipids are synthesized from the precursor phosphatidate via the liponucleotide intermediate CDP-diacylglycerol. As cells exhaust nutrients and progress into the stationary phase, phosphatidate is channeled via diacylglycerol to the synthesis of triacylglycerol. The CHO1 -encoded phosphatidylserine synthase, which catalyzes the committed step in Membrane Phospholipid synthesis via CDP-diacylglycerol, and the PAH1 -encoded phosphatidate phosphatase, which catalyzes the committed step in triacylglycerol synthesis are regulated throughout cell growth by genetic and biochemical mechanisms to control the balanced synthesis of Membrane Phospholipids and triacylglycerol. The loss of phosphatidate phosphatase activity (e.g., pah1 Δ mutation) increases the level of phosphatidate and its conversion to Membrane Phospholipids by inducing Cho1 expression and phosphatidylserine synthase activity. The regulation of the CHO1 expression is mediated through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2–Ino4/Opi1) regulatory circuit. Consequently, phosphatidate phosphatase activity regulates Phospholipid synthesis through the transcriptional regulation of the phosphatidylserine synthase enzyme.
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Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for Membrane Phospholipid synthesis
The Journal of biological chemistry, 2017Co-Authors: Gil-soo Han, George M. CarmanAbstract:Abstract The PAH1-encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae, exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of Membrane Phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in Phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1-encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major Phospholipids via the CDP–diacylglycerol pathway. The lack of PAP in the pah1Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1. Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1Δ mutant is induced through the inositol-sensitive upstream activation sequence (UASINO), a cis-acting element for the phosphatidate-controlled Henry (Ino2–Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UASINO mutation suppressed pah1Δ effects on lipid synthesis, nuclear/endoplasmic reticulum Membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1-encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for Membrane Phospholipid synthesis.