title: Mitochondrial phospholipase A2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling.
abstract: Homeostasis of reactive oxygen species (ROS) in cardiomyocytes is critical for elucidation of normal heart physiology and pathology. Mitochondrial phospholipases A2 (mt-PLA2) have been previously suggested to be activated by ROS. Therefore, we have attempted to elucidate physiological role of such activation. We have found that function of a specific i-isoform of mitochondrial phospholipase A2 (mt-iPLA2) is activated by tert-butylhydroperoxide in isolated rat heart mitochondria. Isoform specificity was judged from the inhibition by bromoenol lactone (BEL), a specific iPLA2 inhibitor. Concomitant uncoupling has been caused by free fatty acids, since it was inhibited by bovine serum albumin. The uncoupling was manifested as a respiration burst accompanied by a slight decrease in mitochondrial inner membrane potential. Since this uncoupling was sensitive to carboxyatractyloside and purine nucleotide di- and tri-phosphates, we conclude that it originated from the onset of fatty acid cycling mediated by the adenine nucleotide translocase (major contribution) and mitochondrial uncoupling protein(s) (minor contribution), respectively. Such a mild uncoupling may provide a feedback downregulation of oxidative stress, since it can further attenuate mitochondrial production of ROS. In conclusion, ROS-induced function of cardiac mt-iPLA2 may stand on a pro-survival side of ischemia-reperfusion injury.
authors.affiliation: Department of Membrane Transport Biophysics, No. 75, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Ježek
authors.forename: M
authors.initials: M
authors.lastname: Jabůrek
authors.forename: J
authors.initials: J
authors.lastname: Zelenka
authors.forename: P
authors.initials: P
authors.lastname: Ježek
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D054522:Group VI Phospholipases A2 / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; D000226:Mitochondrial ADP, ATP Translocases; D020122:tert-Butylhydroperoxide; D054522:Group VI Phospholipases A2; C535117:Pla2g6 protein, rat