Decreased iPLA2γ expression induces lipid peroxidation and cell death and sensitizes cells to oxidant-induced apoptosis
Our previous studies showed that renal proximal tubular cells (RPTC) express Ca2+-independent phospholipase A2γ (iPLA2γ) in endoplasmic reticulum (ER) and mitochondria and that iPLA2γ prevents and/or repairs lipid peroxidation induced by oxidative stress. Our present studies determined the importanc...
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Published in | Journal of lipid research Vol. 49; no. 7; pp. 1477 - 1487 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
01.07.2008
American Society for Biochemistry and Molecular Biology Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Our previous studies showed that renal proximal tubular cells (RPTC) express Ca2+-independent phospholipase A2γ (iPLA2γ) in endoplasmic reticulum (ER) and mitochondria and that iPLA2γ prevents and/or repairs lipid peroxidation induced by oxidative stress. Our present studies determined the importance of iPLA2γ in mitochondrial and cell function using an iPLA2γ-specific small hairpin ribonucleic acid (shRNA) adenovirus. iPLA2γ expression and activity were decreased in the ER by 24 h and in the mitochondria by 48 h compared with scrambled shRNA adenovirus-treated cells. Lipid peroxidation was elevated by 2-fold at 24 h and remained elevated through 72 h in cells with decreased iPLA2γ. Using electrospray ionization-mass spectrometry, primarily phosphatidylcholines and phosphatidylethanolamines were increased in iPLA2γ-shRNA-treated cells. At 48 h after exposure to the iPLA2γ shRNA, uncoupled oxygen consumption was inhibited by 25% and apoptosis was observed at 72 and 96 h. RPTC with decreased iPLA2γ expression underwent apoptosis when exposed to a nonlethal concentration of the oxidant tert-butyl hydroperoxide (TBHP). Exposure of control cells to a nonlethal concentration of TBHP induced iPLA2γ expression in RPTC. These results suggest that iPLA2γ is required for the prevention and repair of basal lipid peroxidation and the maintenance of mitochondrial function and viability, providing further evidence for a cytoprotective role for iPLA2γ from oxidative stress. |
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Bibliography: | G. R. Kinsey and J. L. Blum contributed equally to this work. Published, JLR Papers in Press, April 8, 2008. To whom correspondence should be addressed. e-mail: schnell@musc.edu |
ISSN: | 0022-2275 1539-7262 |
DOI: | 10.1194/jlr.M800030-JLR200 |