中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《生命科学》 2004, (2): 73-
V-ATPase: 结构、功能及其在肿瘤细胞中的作用
卢小东1, 覃文新2*, 杨胜利1,2
1 江苏大学生命科学院,镇江 212013;2上海交通大学医学院上海市肿瘤研究所癌基因及相关基因国家重点实验室,上海 200032
摘 要:真核细胞膜及管泡细胞器膜上广泛分布一种与H+主动转运有关的蛋白——V-ATPase。V-ATPase的结构由跨膜的V0和细胞质内的V1两个亚单位组成,前者为H+提供通道,后者能分解ATP,为逆浓度梯度转运H+提供能量。V0和V1只有在聚合时,V-ATPase全酶才有功能。肿瘤细胞中V-ATPase的过度表达或过度活跃,遏制了由酵解增强乳酸聚集导致的细胞内酸化趋势,使细胞避免了凋亡的命运。而H+排至细胞外,改变蛋白水解酶的活性,使细胞外基质分解增强,细胞更有侵袭力。肿瘤细胞的V-ATPase可望成为抑制细胞增生、扩散的有效靶点。
关键词:V-ATPase;肿瘤
 
V-ATPase: structure, function and roles in tumor cells
LU Xiao-Dong1, QIN Wen-Xin2*, YANG Sheng-Li1,2
1 School of Life Sciences, Jiangsu University, Zhenjiang 212013, China; 2 National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Abstract: The vacuolar (H+)-ATPase is a membrane-related protein in eukaryotic cells which can pump H+ outside of the cells or into the lumens of some vacuolar organelles to maintain the cytoplasmic pH in a relatively stable neutral level which is essential for the cells?survival and to acidify some intracellular apartments which is necessary for the functions of endosomes, lysosomes and Golgi apparatus. The holoenzyme is composed of the membrane sector V0 and the cytoplasmic sector V1. Only when V1 attaches to V0, can H+ go through the transmembrane hydrophilic path of V0 to the opposite side of the membrane, using the energy from the ATP hydrolyzed by V1. The main regulation of the activity of the holoenzyme relies on the reversible attachment or disattachment of V1 and V0. The defectiveness of any subunit, the effects of some non-V-ATPase proteins or the small molecular inhibitors, the changes of the microenvironment around the cells or the changes of the metabolism within the cells will interrupt the activity of the holoenzyme which will then lead to the re-distribution of H+ and change the fate of the cells in the end. Tumor cells are inclined to be intracellular acidified resulted from changed metabolism which may be activated by loss of the oxygen supply. Nonetheless, the over-activated V-ATPase helps the cells to maintain cytoplasmic pH normal and therefore to escape the fate of apoptosis. The extracellullar over-leaked H+ will re-build the crosstalk between the cells and the ECM (extracellular matrix) which will in turn interfere many signal pathways inside the cells. Following that, many behaviors of the tumor cells like invasion, angiogenesis or multi-drug-resistant were modified to be optimized for the survival of the cells. Thus, the over-activated V-ATPase may be an initial and enhancing factor of the aggressive growth of tumors and therefore is qualified to be a candidate target for the therapy of tumor.
Key words: V-ATPase; tumor
 
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