INHIBITION OF CARDIOLIPIN BIOSYNTHESIS IN THE HYPOXIC RAT-HEART

Cardiolipin is the principal polyglycerophospholipid in the heart. The effect of hypoxia on cardiolipin biosynthesis was investigated in isolated rat hearts perfused in the Langendorff mode. Hearts were pulsed-labeled for 60 min with 0.1 mM [1,(3)-H-3]glycerol in Krebs Henseleit buffer saturated with either 95% O-2/5% CO2 (control) or 95% N-2/5% CO2 (hypoxic). Radioactivity incorporated into phosphatidylglycerol and cardiolipin were reduced 88% (P < .05) and 79% (P < .05), respectively, in hypoxic hearts compared to controls. In other experiments, hearts were pulse-labeled for 15 min with 1.4 mM [P-32]P-i in Krebs Henseleit buffer saturated with 95% O-2/5% CO2 and subsequently perfused for 60 min under control or hypoxic conditions. The radioactivity incorporated into CDP-1,2-diacyl-sn-glycerol, phosphatidylglycerol, and cardiolipin were reduced 61% (P < .05), 71% (P < .05), and 70% (P < .05), respectively, in the hypoxic hearts compared to controls, indicating a decreased formation of CDP-1,2-diacyl-sn-glycerol in the hypoxic heart. The activities of the enzymes involved in cardiolipin biosynthesis and the cardiac pool sizes of cardiolipin, phosphatidylglycerol, and CDP-1,2-diacyl-1,2-diacyl-sn-glycerol were unaltered between hypoxic and control hearts. In contrast, cardiac adenosine-5'-triphosphate and CPT levels were decreased 94% (P < .05) and 92% (P < .05), respectively, in hypoxic hearts compared to controls. We postulate that the biosynthesis of the cardiac polyglycerophospholipid cardiolipin may be inhibited by a decreased adenosine-5'-triphosphate and cytidine-5'-triphosphate level in the heart.