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

大鼠胞质乙酰辅酶A水解酶活性与病理生理状态的关系

基本信息

批准号：
07807018
负责人：
ISOHASHI Fumihide
金额：
$ 1.47万
依托单位：
St. Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

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.

在早期糖尿病、胆固醇喂养、微粒体3-羟基-3-甲基戊二酰辅酶a还原酶（CS-514）的有效竞争性抑制剂和降血脂药物[α -（红氯苯氧基）异丁酸，CPIB)治疗组中，胞浆乙酰辅酶a水解酶的活性增加。胆固醇喂养的大鼠经消胆胺处理后，酶活性恢复到初始水平。在慢性糖尿病患者中，酶活性在正常范围内，但当给予胆固醇饮食、CPIB或CS-514时，酶活性显著增加。酶活性的增加与酶联免疫吸附试验测定的酶蛋白的增加有关。这些结果表明，该酶在维持胆固醇代谢的胞浆乙酰辅酶a浓度和CoASH库之间的平衡中具有生理作用。东流雄性白化病大鼠在饲粮中添加0.06% 3′-甲基-4-二甲基-氨基偶氮苯（3′-Me-DAB） 20周后，肝脏胞浆乙酰辅酶a水解酶活性在第2周降至初始水平的1 / 3左右，在第7周恢复到对照水平，在第20周再次降至对照水平的1 / 10左右。酶活性的变化与酶蛋白含量的变化是一致的。3’- me - dab耐药大鼠在饲喂含3’- me - dab饮食20周后，酶活性和酶蛋白保持在正常范围内，宏观上未检出肿瘤。有趣的是，在偶氮染料诱导的肝癌发生过程中，这种酶活性的双相变化与众所周知的γ -谷氨酰转肽酶活性的变化呈负相关。