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首页> 外文期刊>American Journal of Physiology >Role of TRPM2 in cell proliferation and susceptibility to oxidative stress
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Role of TRPM2 in cell proliferation and susceptibility to oxidative stress

机译：TRPM2在细胞增殖和氧化应激敏感性中的作用

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摘要

The transient receptor potential (TRP) channel TRPM2 is an ion channel that modulates cell survival. We report here that full-length (TRPM2-L) and short (TRPM2-S) isoform expression was significantly increased in human neuroblastoma com-pared with adrenal gland. To differentiate the roles of TRPM2-L and TRPM2-S in cell proliferation and survival, we established neuroblas-toma SH-SY5Y cell lines stably expressing either TRPM2 isoform or empty vector. Cells expressing TRPM2-S showed significantly en-hanced proliferation, downregulation of phosphatase and tensin ho-molog (PTEN), and increased protein kinase B (Akt) phosphorylation and cell surface glucose transporter 1 (Glut1) compared with cells expressing TRPM2-L or empty vector. ERK phosphorylation was increased, and forkhead box O 3a (FOXO3a) levels were decreased. Inhibitor studies demonstrated that enhanced proliferation was depen-dent on phosphatidylinositol 3-kinase/Akt, ERK, and NADPH oxi-dase activation. On the other hand, TRPM2-S-expressing cells were significantly more susceptible to cell death induced by low H2O2 concentrations (50-100 μM), whereas TRPM2-L-expressing cells were protected. This was associated with a significant increase in FOXO3a, MnSOD (SOD2), and membrane Glut1 in TRPM2-L-expressing cells compared with TRPM2-S expressing cells. We con-clude that TRPM2 channels occupy a key role in cell proliferation and survival following oxidative stress in neuroblastoma. Our results suggest that overexpression of TRPM2-S results in increased prolif-eration through phosphatidylinositol 3-kinase/Akt and ERK path-ways, while overexpression of TRPM2-L confers protection against oxidative stress-induced cell death through FOXO3a and SOD. TRPM2 channels may represent a novel future therapeutic target in diseases involving oxidative stress.
机译：瞬时受体电位（TRP）通道TRPM2是调节细胞存活的离子通道。我们在这里报告在人类神经母细胞瘤与肾上腺相比，全长（TRPM2-L）和短（TRPM2-S）同工型表达显着增加。为了区分TRPM2-L和TRPM2-S在细胞增殖和存活中的作用，我们建立了稳定表达TRPM2亚型或空载体的神经鞘瘤SH-SY5Y细胞系。与表达TRPM2-L的细胞相比，表达TRPM2-S的细胞显示出明显增强的增殖，磷酸酶和张力蛋白同源性（PTEN）下调，并且蛋白激酶B（Akt）磷酸化和细胞表面葡萄糖转运蛋白1（Glut1）增强。空向量。 ERK磷酸化增加，叉头盒O 3a（FOXO3a）含量降低。抑制剂研究表明，增强的增殖取决于磷脂酰肌醇3-激酶/ Akt，ERK和NADPH氧化酶的活化。另一方面，表达TRPM2-S的细胞更容易受到低浓度H2O2（50-100μM）诱导的细胞死亡的影响，而表达TRPM2-L的细胞受到保护。与表达TRPM2-S的细胞相比，这与表达TRPM2-L的细胞中FOXO3a，MnSOD（SOD2）和膜Glut1的显着增加有关。我们得出结论，神经母细胞瘤中的氧化应激后，TRPM2通道在细胞增殖和存活中起关键作用。我们的结果表明，TRPM2-S的过表达导致通过磷脂酰肌醇3-激酶/ Akt和ERK途径的增殖增加，而TRPM2-L的过表达则赋予保护作用，使其免受FOXO3a和SOD引起的氧化应激诱导的细胞死亡。 TRPM2通道可能代表了涉及氧化应激疾病的新型治疗靶标。

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