Relationship between Cytosolic Acetyl-CoA Hydrolase Activity and Pathophysiological states of rats

在早期糖尿病、胆固醇喂养、微粒体3-羟基-3-甲基戊二酰-CoA还原酶（CS-514）的有效竞争性抑制剂和降血脂药物[α-（对-苯氧基）异丁酸（CPIB）]处理组中，细胞溶质乙酰-CoA水解酶的活性增加。胆固醇喂养大鼠的考来烯胺治疗使酶活性恢复到初始水平。在慢性糖尿病中，酶活性在正常范围内，但在给予胆固醇饮食、CPIB或CS-514时显著增加。通过这些治疗的酶活性的增加与酶联免疫吸附测定法测定的酶蛋白的增加有关。这些结果表明，该酶在维持细胞内乙酰辅酶A浓度和胆固醇代谢的CoASH池之间的平衡中具有生理作用。当给雄性白化病大鼠喂含0.06% 3 '-甲基-4-二甲基氨基偶氮苯的饲料时，（3 '-Me-DAB）20周后，其肝脏中的胞质乙酰辅酶A水解酶活性在第2周降低至初始水平的约三分之一，在第7周恢复到对照水平，然后在第20周再次下降到对照的十分之一。酶活性的这些变化与ELISA测定的酶蛋白量的变化平行，然而，在3 ′-Me-DAB抗性大鼠中，在给予含3 ′-Me-DAB的饮食20周期间，酶活性和酶蛋白保持在正常范围内，肉眼未检测到肿瘤。有趣的是，这种酶活性的双相变化与众所周知的偶氮染料诱导的肝癌发生过程中γ-谷氨酰转肽酶活性的变化呈负相关。

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.