Ikeda Yoshitaka, Taniguchi Naoyuki
Division of Molecular Cell Biology, Department of Biomolecular Sciences, Saga University Faculty of Medicine, Japan.
Methods Enzymol. 2005;401:408-25. doi: 10.1016/S0076-6879(05)01025-6.
gamma-Glutamyltranspeptidase is a heterodimeric glycoprotein that catalyzes the transpeptidation and hydrolysis of the gamma-glutamyl group of glutathione and related compounds. It is known that the enzyme plays a role in the metabolism of glutathione and in salvaging constituents of glutathione. In the adult animal, high levels of gamma-glutamyltranspeptidase are constitutively expressed in the kidney, intestine, and epididymis. On the other hand, although gamma-glutamyltranspeptidase is up-regulated in the liver during the perinatal stage, its expression is nearly undetectable in the adult. In addition, it has long been observed that the intake of certain xenobiotics, including carcinogens and drugs, induces the hepatic expression of the enzyme. This induction seems to be associated with both transcriptional regulation and the growth of certain types of cells in the injured liver. A number of studies have been carried out to explain the mechanism by which gamma-glutamyltranspeptidase expression is regulated. 5'-Untranslated regions of mRNAs of the enzyme differ in a tissue-specific manner but share a common protein coding region, and the tissue-specific and developmental stage-specific expression, as well as hepatic induction, are conferred by different promoters. As suggested by the capability of enzymatic activity-independent induction of osteoclasts, the expression of gamma-glutamyltranspeptidase may also be involved in various biological processes that are not directly associated with glutathione metabolism. This chapter briefly summarizes studies to date concerning the tissue-specific expression and induction of gamma-glutamyltranspeptidase and transcriptional regulation by the multiple promoter system is discussed.
γ-谷氨酰转肽酶是一种异二聚体糖蛋白，可催化谷胱甘肽及相关化合物的γ-谷氨酰基的转肽作用和水解作用。已知该酶在谷胱甘肽的代谢以及谷胱甘肽成分的挽救中发挥作用。在成年动物中，肾脏、肠道和附睾中组成性表达高水平的γ-谷氨酰转肽酶。另一方面，虽然γ-谷氨酰转肽酶在围产期肝脏中上调，但其在成年期的表达几乎检测不到。此外，长期以来人们观察到，摄入某些外源性物质，包括致癌物和药物，会诱导该酶在肝脏中的表达。这种诱导似乎与转录调控以及受损肝脏中某些类型细胞的生长有关。已经进行了许多研究来解释γ-谷氨酰转肽酶表达的调控机制。该酶mRNA的5'-非翻译区以组织特异性方式不同，但共享一个共同的蛋白质编码区，并且组织特异性和发育阶段特异性表达以及肝脏诱导是由不同的启动子赋予的。正如破骨细胞酶活性非依赖性诱导的能力所表明的那样，γ-谷氨酰转肽酶的表达也可能参与各种与谷胱甘肽代谢不直接相关的生物学过程。本章简要总结了迄今为止关于γ-谷氨酰转肽酶的组织特异性表达和诱导以及多启动子系统转录调控的研究。
