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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Oxidative stress reduces Na+/H+ exchange (NHE) activity in a biliary epithelial cancer cell line (Mz-Cha-1).
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Oxidative stress reduces Na+/H+ exchange (NHE) activity in a biliary epithelial cancer cell line (Mz-Cha-1).

机译:氧化应激会降低胆道上皮癌细胞系(Mz-Cha-1)中的Na + / H +交换(NHE)活性。

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摘要

In cholangiocarcinogenesis, chronic inflammation and oxidative stress play a key role. The Na(+)/H(+) exchanger (NHE) forms a potential link between control of intra- and pericellular pH and tumor development. Therefore, the effects of oxidant stress were determined by the use of tert-butyl hydroperoxide (t-BOOH) on Na(+)/H(+) exchange in a biliary epithelial cancer cell line (Mz-Cha-1). The cells were exposed to the hydroperoxide and the rate of recovery from acidosis was determined by the use of the pH-sensitive fluorochrome 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF/AM). t-BOOH reduced Na(+)/H(+) exchange activity in a dose-dependent manner. At 4 mM t-BOOH, Na(+)/H(+) exchange activity was virtually absent. This was accompanied by an increase in cytotoxicity (MTT assay). Glutathione repletion and intracellular Ca(++) chelation partially restored the Na(+)/H(+) exchange activity. Hydroperoxide seemed neither to alter the intracellular signal transduction pathways (cAMP and Ca(++) oscillations) nor the membrane distribution of the exchanger (immunostaining). Decrease in Na(+)/H(+) exchange activity in this model of oxidant stress may represent an early perturbation of membrane function, and the functional integrity of Na(+)/H(+) exchange could therefore be dependent on the glutathione redox system.
机译:在胆管癌发生中,慢性炎症和氧化应激起关键作用。 Na(+)/ H(+)交换剂(NHE)形成控制细胞内和细胞外pH值与肿瘤发展之间的潜在联系。因此,氧化应激的影响是通过使用叔丁基氢过氧化物(t-BOOH)对胆管上皮癌细胞系(Mz-Cha-1)中Na(+)/ H(+)交换的影响来确定的。使细胞暴露于氢过氧化物,并通过使用pH敏感的荧光染料2',7'-双(羧乙基)-5(6)-羧基荧光素乙酰氧基甲基酯(BCECF / AM)确定酸中毒的恢复率。 t-BOOH以剂量依赖性方式降低Na(+)/ H(+)交换活性。在4 mM t-BOOH时,实际上不存在Na(+)/ H(+)交换活性。这伴随着细胞毒性的增加(MTT测定)。谷胱甘肽的补充和细胞内Ca(++)螯合部分恢复Na(+)/ H(+)交换活动。氢过氧化物似乎既不改变细胞内信号转导途径(cAMP和Ca(++)振荡),也不改变交换器的膜分布(免疫染色)。在这种氧化应激模型中,Na(+)/ H(+)交换活性的降低可能代表膜功能的早期扰动,因此Na(+)/ H(+)交换的功能完整性可能取决于谷胱甘肽氧化还原系统。

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