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甘油醛-3-磷酸脱氢酶在神经退行性变和细胞凋亡信号传导中的作用

Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling.

作者信息

Tatton W G, Chalmers-Redman R M, Elstner M, Leesch W, Jagodzinski F B, Stupak D P, Sugrue M M, Tatton N A

机构信息

Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA.

出版信息

J Neural Transm Suppl. 2000(60):77-100. doi: 10.1007/978-3-7091-6301-6_5.

DOI:10.1007/978-3-7091-6301-6_5
PMID:11205159
Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a well-studied glycolytic enzyme that plays a key role in energy metabolism. GAPDH catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate in the glycolytic pathway. As part of the conversion, GAPDH converts NAD+ to the high-energy electron carrier NADH. GAPDH has been referred to as a "housekeeping" protein and based on the view that GAPDH gene expression remains constant under changing cellular conditions, the levels of GAPDH mRNA have frequently been used to normalize northern blots. In recent years, that view has changed since GAPDH is now known to contribute to a number of diverse cellular functions unrelated to glycolysis. Normative functions of GAPDH now include nuclear RNA export, DNA replication, DNA repair, exocytotic membrane fusion, cytoskeletal organization and phosphotransferase activity. Pathologically, GAPDH has been implicated in apoptosis, neurodegenerative disease, prostate cancer and viral pathogenesis (see Sirover (1999) for a recent review of GAPDH functions). Most recently, it has been shown that GAPDH is a target for deprenyl related compounds (Carlile et al., 2000; Kragten et al., 1998) and may contribute to the neuroprotection offered by those compounds.

摘要

甘油醛-3-磷酸脱氢酶(GAPDH)是一种经过充分研究的糖酵解酶,在能量代谢中起关键作用。GAPDH在糖酵解途径中催化甘油醛-3-磷酸转化为1,3-二磷酸甘油酸。作为该转化过程的一部分,GAPDH将NAD⁺转化为高能电子载体NADH。GAPDH一直被称为“管家”蛋白,基于GAPDH基因表达在细胞条件变化时保持恒定的观点,GAPDH mRNA的水平经常被用于标准化Northern印迹。近年来,这种观点发生了变化,因为现在已知GAPDH参与许多与糖酵解无关的不同细胞功能。GAPDH的正常功能现在包括核RNA输出、DNA复制、DNA修复、胞吐膜融合、细胞骨架组织和磷酸转移酶活性。在病理方面,GAPDH与细胞凋亡、神经退行性疾病、前列腺癌和病毒发病机制有关(有关GAPDH功能的最新综述,请参见Sirover(1999))。最近,已经表明GAPDH是去甲异喹啉相关化合物的作用靶点(Carlile等人,2000年;Kragten等人,1998年),并且可能有助于这些化合物提供的神经保护作用。

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