Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori
Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori
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DOI：
10.1006/mpat.2001.0446
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发表时间：
2001-07-01
影响因子：
3.8
通讯作者：
Kondo, T
中科院分区：
文献类型：
--
作者：
Kimura, M;Goto, S;Kondo, T
幽门螺杆菌空泡细胞毒素（VacA）被认为是诱发胃病的因素之一。我们之前的研究表明，VacA导致人胃上皮细胞胞内ATP水平下降，这表明VacA损害线粒体膜电位，随后导致能量代谢下降(Kimura et al., Microb。Pathog。， 1999, 26。45-52)。在本研究中，我们研究了ATP水平的降低是否会影响谷胱甘肽的代谢，其中其合成和流出依赖于ATP。用120 nM VacA处理AZ-521人胃上皮细胞6小时后，氧化谷胱甘肽（GSSG）的外排呈剂量和时间依赖性。经VacA处理的细胞的GSSG外排量和谷胱甘肽（GSH）合成量分别约为对照组的50%和70%。胞内谷胱甘肽的周转率也受到VacA的抑制。经VacA预处理后，再与H2O2孵育，细胞活力在6 h和12 h分别下降50%和70%。这些结果表明，VacA损害了胃上皮细胞对GSH的代谢，从而削弱了细胞对氧化应激或GSH对细胞氧化还原调节的抵抗力。(C) 2001学术出版社。
Helicobacter pylori vacuolating cytotoxin (VacA) is believed to be one of the factors that induces gastric disease. Our previous study indicated that VacA causes a decrease in the intracellular ATP level in human gastric epithelial cells, suggesting to impair mitochondrial membrane potential followed by a decrease in energy metabolism (Kimura et al., Microb. Pathog., 1999, 26. 45-52). In the present study, we investigated whether the decrease in ATP level affects glutathione metabolism, in which its synthesis and efflux are ATP-dependent. Treatment of AZ-521 human gastric epithelial cells with 120 nM VacA for 6 h suppressed the afflux of oxidized glutathione (GSSG) in a dose-and time-dependent manner. The efflux of GSSG from the cells and glutathione (GSH) synthesis of cells treated with VacA were approximately 50 and 70% of those of the control, respectively. The turnover rate of intracellular GSH was also suppressed by VacA. Viability of the cells pretreated with VacA, then further incubated with H2O2, was decreased by 50% at 6 h and 70% at 12 h. These results suggested that VacA impairs GSH metabolism in the gastric epithelial cells, which weakens the resistance of the cells against oxidative stress or cellular redox regulation by GSH. (C) 2001 Academic Press.