Phospholipase A2: a potentially important determinant of adenosine triphosphate levels during hypoxic-reoxygenation tubular injury.

Journal of the American Society of Nephrology : JASN
Richard A ZagerK Burkhart

Abstract

During the course of O2 deprivation-induced proximal tubular injury, profound alterations in ATP homeostasis exist. This study sought to characterize direct cellular determinants of these abnormalities further. Mouse proximal tubular segments (PTS) were isolated and their adenine nucleotide profiles were determined during hypoxic-reoxygenation injury. The extent of oxidant stress, Ca2+ overload, cytoskeletal disruption, and phospholipase activity were experimentally manipulated by H2O2, Ca2+ ionophore, cytochalasin D, or PLA2 addition, respectively. Hypoxia induced the expected deterioration in adenylate profiles, and a persistent defect in ATP homeostasis was observed during reoxygenation (decreased ATP/ADP ratios and absolute ATP content). H2O2, Ca2+ ionophore, and cytochalasin D had no significant impact on adenylate profiles. However, doses of PLA2 that had no overt effect on normal tubules caused 50 to 75% reductions in both hypoxic and reoxygenation ATP/ADP ratios and absolute ATP content. This effect was completely reproduced by the addition of arachidonic acid (C20:4). No other test fatty acid (C16:0, C18:1, C18:3) reproduced this result. Despite its profound negative impact on hypoxic/reoxygenation ATP concentrations, ...Continue Reading

Citations

Sep 24, 1999·Current Opinion in Nephrology and Hypertension·D Portilla
Jun 19, 2003·The Journal of Biological Chemistry·Andres A Caro, Arthur I Cederbaum
Feb 6, 2004·The Journal of Biological Chemistry·Shama AhmadCarl W White
Aug 26, 1998·Biochimica Et Biophysica Acta·A Szewczyk, S Pikuła
Apr 11, 2001·The Journal of Biological Chemistry·T N MeyerS K Nigam
Dec 22, 2004·Kidney International·Richard A ZagerSherry Y Hanson
Aug 3, 2000·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·R A Zager
Oct 7, 2008·Toxicon : Official Journal of the International Society on Toxinology·Daniela N AmoraHelena S A Monteiro

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