title: Inhibition of cardiolipin biosynthesis in the hypoxic rat heart.
abstract: 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)-3H]glycerol in Krebs Henseleit buffer saturated with either 95% O2/5% CO2 (control) or 95% N2/5% 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 [32P]Pi in Krebs Henseleit buffer saturated with 95% O2/5% 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.
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Cheng
authors.forename: G M
authors.initials: GM
authors.lastname: Hatch
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002308:Cardiolipins / Q000096:biosynthesis*; D003567:Cytidine Diphosphate Diglycerides / Q000378:metabolism; D003570:Cytidine Triphosphate / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002308:Cardiolipins; D003567:Cytidine Diphosphate Diglycerides; D010715:Phosphatidylglycerols; D003570:Cytidine Triphosphate; D000255:Adenosine Triphosphate; D009713:Nucleotidyltransferases; C022348:phosphatidate cytidylyltransferase