Phospholipid metabolism in cardiomyopathic hamster heart cells.
We demonstrated that the activities of phosphatidylinositide-specific phospholipase C, inositol 1,4,5-trisphosphate (IP3) kinase, and IP3 phosphatase were enhanced in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) in comparison to control hamsters (F1b). Release of both arachidonic acid and prostacyclin was markedly enhanced by norepinephrine in the cardiomyopathic hamsters. Phospholipase C in heart has high substrate specificity to phosphatidylinositol. IP3 production was markedly enhanced in the cardiomyopathic hamsters. We also determined the intracellular calcium concentration, which was higher in BIO 53.58 hamsters than in BIO 14.6 hamsters at 5-20 weeks of age. There was no significant difference in the intracellular calcium level between F1b and BIO 14.6 hamsters at 5 weeks of age. These results suggest that phosphatidylinositol turnover stimulated by norepinephrine may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in BIO 53.58 hamsters, some mechanism such as the sarcoplasmic reticulum, which controls the intracellular calcium level, may deteriorate in function. We concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes.
Kawaguchi
H
H
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Shoki
M
M
Sano
H
H
Kudo
T
T
Sawa
H
H
Okamoto
H
H
Sakata
Y
Y
Yasuda
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D002384:Catalysis; D006224:Cricetinae; D004789:Enzyme Activation; D008297:Male; D008647:Mesocricetus; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D010716:Phosphatidylinositols; D010743:Phospholipids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D010738:Type C Phospholipases; D009638:Norepinephrine