糖尿病转基因小鼠中的氨基脲敏感胺氧化酶

Semicarbazide-sensitive amine oxidase in transgenic mice with diabetes.

作者信息

Gokturk C, Nordquist J, Sugimoto H, Forsberg-Nilsson K, Nilsson J, Oreland L

机构信息

Section of Pharmacology, Department of Neuroscience, Uppsala University, Box 593, Biomedicum, 751 24 Uppsala, Sweden.

出版信息

Biochem Biophys Res Commun. 2004 Dec 17;325(3):1013-20. doi: 10.1016/j.bbrc.2004.10.140.

DOI:10.1016/j.bbrc.2004.10.140

PMID:15541390

Abstract

Semicarbazide-sensitive amine oxidase (SSAO) activity in plasma is increased in diabetes, and in particular, in diabetic patients with vascular complications. It has been speculated that SSAO is involved in the development of such complications due to the production of cytotoxic compounds. In this work, we have induced diabetes in a previously described mouse-model, overexpressing SSAO in smooth muscle cells. SSAO activity was estimated as well as expression of the endogenous mouse gene and human transgene using real-time PCR. Diabetes induced an increase in SSAO activity in serum, kidney, and adipose tissue of transgenic animals. An inverse correlation between SSAO activity and mouse SSAO mRNA levels was observed in transgenic animals with diabetes. These results further support the suggestion of a negative feedback control of the SSAO gene expression. The increased SSAO activity in diabetes is most likely dependent on post-transcriptional modifications or activation of existing inactive enzyme molecules.

摘要

糖尿病患者，尤其是患有血管并发症的糖尿病患者，其血浆中的氨基脲敏感性胺氧化酶（SSAO）活性会升高。据推测，由于细胞毒性化合物的产生，SSAO参与了此类并发症的发展。在这项研究中，我们在先前描述的小鼠模型中诱导糖尿病，该模型在平滑肌细胞中过表达SSAO。使用实时PCR估计了SSAO活性以及内源性小鼠基因和人类转基因的表达。糖尿病导致转基因动物血清、肾脏和脂肪组织中的SSAO活性增加。在患有糖尿病的转基因动物中，观察到SSAO活性与小鼠SSAO mRNA水平呈负相关。这些结果进一步支持了SSAO基因表达存在负反馈控制的观点。糖尿病中SSAO活性增加很可能依赖于转录后修饰或现有无活性酶分子的激活。