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

摘要: During the course of O2 deprivation-induced proximal tubular injury, profound alterations in ATP homeostasis exist. This study sought to characterize direct cellular determinants these abnormalities further. Mouse segments (PTS) were isolated and their adenine nucleotide profiles determined during hypoxic-reoxygenation injury. The extent oxidant stress, Ca2+ overload, cytoskeletal disruption, phospholipase activity experimentally manipulated by H2O2, ionophore, cytochalasin D, or PLA2 addition, respectively. Hypoxia induced expected deterioration adenylate profiles, a persistent defect was observed reoxygenation (decreased ATP/ADP ratios absolute content). D had no significant impact on profiles. However, doses that overt effect normal tubules caused 50 75% reductions both hypoxic content. completely reproduced addition arachidonic acid (C20:4). No other test fatty (C16:0, C18:1, C18:3) this result. Despite its negative hypoxic/reoxygenation concentrations, C20:4 each decreased lethal cell injury (lactate dehydrogenase release), as previously reported. not mechanistically linked, because C18:1 C18:3 protective action without altering Ouabain, mannitol, plasma membrane "scavenger" therapy (albumin) did improve posthypoxic/PLA2-induced depressions ATP. modest decrease posthypoxic tubule oxygen consumption, compared controls. It concluded that: (1) can be major determinant concentrations injury; (2) is mediated via release; (3) primary mitochondrial production, rather than increased likely responsible for action.