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链脲佐菌素诱导的糖尿病大鼠肝脏碳酸酐酶同工酶的差异调节

Differential regulation of hepatic carbonic anhydrase isozymes in the streptozotocin-diabetic rat.

作者信息

Dodgson S J, Watford M

机构信息

Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6085.

出版信息

Arch Biochem Biophys. 1990 Mar;277(2):410-4. doi: 10.1016/0003-9861(90)90597-r.

DOI:10.1016/0003-9861(90)90597-r
PMID:2106833
Abstract

Most work with the male rat liver carbonic anhydrase isozymes in the past decade has centered on the cytosolic CA III and the mitochondrial CA V. This paper reports that the relative activity of both isozymes is altered in streptozotocin-diabetes. Carbonic anhydrase activity of perfused liver homogenates and disrupted, isolated mitochondria was measured by the mass spectrometric 18O decay technique at 37 degrees C. The contributions of the different isozymes were determined based on intracellular location and sensitivity to acetazolamide inhibition. Diabetes resulted in a twofold increase in the activity of CA V but a halving in the activity of CA III. This is the first time that liver CA V has been shown to be altered by physiological stress. The total carbonic anhydrase activity in the diabetic rat liver was unaltered compared with control rats; however, CA III never accounted for more than 50% of this activity. Since CA isozymes I, II, and IV together account for 30% of the CA activity in control rats and 70% in diabetic rats it is concluded that one or more of these isozymes is subject to regulation in the diabetic male rat. The increase in CA V during diabetes is in accord with this isozyme having an important function in provision of substrate for hepatic gluconeogenesis and ureagenesis.

摘要

在过去十年中,对雄性大鼠肝脏碳酸酐酶同工酶的研究大多集中在胞质CA III和线粒体CA V上。本文报道,链脲佐菌素诱导的糖尿病会改变这两种同工酶的相对活性。采用质谱18O衰变技术在37℃下测定灌注肝匀浆以及破碎、分离的线粒体的碳酸酐酶活性。根据细胞内定位和对乙酰唑胺抑制的敏感性确定不同同工酶的贡献。糖尿病导致CA V活性增加两倍,但CA III活性减半。这是首次发现肝脏CA V会因生理应激而发生改变。与对照大鼠相比,糖尿病大鼠肝脏中的总碳酸酐酶活性未发生改变;然而,CA III在该活性中所占比例从未超过50%。由于CA同工酶I、II和IV在对照大鼠的CA活性中占30%,在糖尿病大鼠中占70%,因此得出结论,这些同工酶中的一种或多种在糖尿病雄性大鼠中受到调控。糖尿病期间CA V的增加与该同工酶在为肝脏糖异生和尿素生成提供底物方面具有重要功能一致。

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