1997 Fiscal Year Final Research Report Summary
Relationship between Cytosolic Acetyl-CoA Hydrolase Activity and Pathophysiological states of rats
| Project/Area Number |
07807018
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
ISOHASHI Fumihide St. Marianna University School of Medicine, Deparment of Biochemistry, Professor, 医学部, 教授 (20115992)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Acetyl-CoA-Hydrolase / Diabetes / Cholesterol / Hepatocarcinogenesis / Rat liver / Enzyme purification / CoA / 3'-Methyl-4-dimethylaminoazobenzene |
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| Research Abstract |
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.
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