P348Effect of intermittent hypobaric hypoxia on the expression of phospholipases A2 and antioxidative enzymes in rat hearts

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Adaptation to intermittent hypobaric hypoxia (IHH) is associated with increased generation of reactive oxygen species (ROS) that is implicated in the protective mechanism against acute ischemia/reperfusion (I/R) injury. On the other hand, the overproduction of ROS can be detrimental during acute I/R. Myocardial antioxidant systems provide defence against excess ROS and cooperate with phospholipases A2 (PLA2) to remove oxidative products of fatty acids (FA). PLA2 hydrolyze FA from membrane phospholipids with increased affinity for peroxidized FA, thereby helping to keep the integrity of cell membranes via deacylation/reacylation cycle. However, PLA2 may contribute to membrane destruction under conditions of energy deprivation during ischemia. The aim of this study was to analyze changes in the expression of cytosolic (cPLA2), calcium-independent (iPLA2) and secretoric (sPLA2) phospholipases, manganese (MnSOD) and copper/zinc superoxide dismutase (Cu/ZnSOD), catalase (CAT), peroxiredoxin 3 (PRX-3) and glutathione peroxidase 4 (GPX-4) at protein and mRNA levels (by Western blotting and Real Time PCR, respectively) in left ventricular myocardium of adult male Wistar rats adapted to IHH (7000 m, 8h/day, 5 weeks). IHH decreased iPLA2 (by 12%), sPLA2 (by 32%), Cu/ZnSOD (by 15%), PRX-3 (by 25%), GPX-4 (by 22%) and increased cPLA2 (by 10%) at the protein level and decreased cPLA2 (by 15%) and sPLA2 (by 22%) at the mRNA level compared with normoxia. Chronic treatment of rats with N-acetylcysteine (100 mg/kg/day) reduced the effect of IHH on iPLA2 expression at the protein level. These data suggest that the IHH-induced decrease of PLA2 expression is ROS dependent. It remains to be determined whether changes of PLA2 expression contribute to the cell membrane integrity under I/R conditions and to the cardioprotective phenotype of IHH rats.

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