|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1997 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1996 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
The activity of cytosolic acetyl-CoA hydrolase increased in the early diabetic, cholesterol-fed, a potent competitive inhibitor of microsomal 3-hydroxy-3-methylglutaryl-CoA reductase (CS-514), and a hypolipidemic drug [alpha- (rho-chlophenoxy) isobutyric acid, CPIB) treated groups. The cholestyramine treatment of cholesterol-fed rats made the enzyme activity return to the initial level. In chronic diabetes, the enzyme activity was within normal range but increased significantly when given the cholesterol-diet, CPIB,or CS-514. An increase in the enzyme activity by these treatments was associated with an increase in enzyme protein determined by enzyme-linked immunosorbent assay. These resuls suggest that this enzyme has a physiological role in the maintenance of the equilibrium between the cytosolic acetyl-CoA concentration and CoASH pool for cholesterol metabolism.
When Donryu male albino rats were given diet containing 0.06% 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB) for 20 weeks, the activity of cytosolic acetyl-CoA hydrolase in their livers decreased to about one-third the initial level in week 2, returned to the control level in week 7, and then decreased again to anout one-tenth of the control in week 20. These changes in enzyme activity were parallel with changes in the amount of enzyme protein determined by ELISA.In 3'-Me-DAB-resistant rats, however, the enzyme activity and enzyme protein remained within the normal range during administration of 3'-Me-DAB-containing diet for 20 weeks and no tumors were detectable macroscopically. Interestingly, the biphasic change in this enzyme activity was inversely associated with the well known change of gamma-glutamyltranspeptidase activity during azo-dye-induced hepatocarcinogenesis.