Effect of hypoxia on choline metabolism and phosphatidylcholine biosynthesis in isolated adult rat ventricular myocytes: effects of trifluoperazine.
The purpose of this study was to test the hypothesis that hypoxia alters choline metabolism in adult rat ventricular myocytes and that this is subject to modification by trifluoperazine. Ventricular myocytes were isolated from adult Wistar rats. Choline uptake and metabolism were examined, using [methyl-3H]choline. Choline metabolism to phosphatidylcholine (PC), an important phospholipid for cellular structure and function, was reduced by mild hypoxia while choline uptake was not altered. Trifluoperazine at 10(-5) or 10(-6) M reduced PC biosynthesis and did not reduce or prevent the effects of hypoxia. Interruption of myocardial metabolism with the combination of carbonyl cyanide m-chlorophenylhydrozone and amobarbital also reduced PC synthesis, although it also reduced choline uptake by the cell. These data indicate that in isolated cardiomyocyte from the adult rat heart that (i) hypoxia impairs PC biosynthesis, (ii) this may be operative in part through inhibition of mitochondrial function, and (iii) trifluoperazine does not act to oppose these effects of hypoxia, but it impairs PC biosynthesis. Thus a component of the membrane phospholipid changes observed with hypoxia may be due to impairment of PC biosynthesis in the cardiomyocyte.
Rabkin
S W
SW
University of British Columbia, Vancouver, Canada.
D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014268:Trifluoperazine / Q000494:pharmacology*
D010713:Phosphatidylcholines; D014268:Trifluoperazine; D003566:Cytidine Diphosphate Choline; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000654:Amobarbital; D002794:Choline