Alterations of phosphoinositide-specific phospholipase C and protein kinase C in the myocardium of spontaneously hypertensive rats.
In order to determine whether phosphoinositide metabolism is altered in hypertensive cardiac hypertrophy, phospholipase C (PLC) and protein kinase C activities were measured in hearts from 4- and 20-week-old spontaneously hypertensive rats (SHR) and age-matched, normotensive Wistar-Kyoto rats (WKY). PLC activities were assayed using phosphatidylinositol (PI) and phosphatidylinositol-4,5-bisphosphate (PIP2) as substrates to assess the substrate specificity. PI-hydrolyzing PLC activity (PI-PLC) was predominantly located in the cytosol, and its activity was similar in both strains. Membrane-bound PIP2-hydrolyzing PLC activity (PIP2-PLC) was significantly lower in 20-week-old SHR than in WKY, but there was no significant difference in soluble PIP2-PLC. Protein kinase C activity was significantly elevated in 20-week-old SHR and Ca2(+)-phospholipid-dependent phosphorylation was observed in the proteins of molecular weight 26, 32, 43, and 95 KDa. In 4-week-old prehypertensive SHR, there were no significant differences in PI-PLC, PIP2-PLC, or protein kinase C activities as compared with age-matched WKY. These data demonstrated that protein kinase C and membrane-bound PIP2-PLC are altered during the period of hypertension development. These alterations may have important roles in the development or maintenance of hypertensive cardiac hypertrophy in SHR.
Makita
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N
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Yasuda
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H
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D006321:Heart / Q000033:anatomy & histology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D010738:Type C Phospholipases / Q000378:metabolism*
D010716:Phosphatidylinositols; D011506:Proteins; D011493:Protein Kinase C; D010738:Type C Phospholipases