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首页> 外文期刊>Acta neurobiologiae experimentalis >Signals mediating Klotho-induced neuroprotection in hippocampal neuronal cells
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Signals mediating Klotho-induced neuroprotection in hippocampal neuronal cells

机译：信号介导Klotho诱导的海马神经元细胞的神经保护

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摘要

The erythropoietin (Epo) receptor (EpoR) is expressed in the brain and was shown to have neuroprotective effects against brain damage in animal models. A recent study indicated that EpoR and its activity are the downstream effectors of Klotho for cytoprotection in the kidney. Thus, we propose that Klotho can stimulate the expression of EpoR in neuronal cells to enhance Epo-mediated protection. H19-7 hippocampal neuronal cells were treated with recombinant Klotho. In H19-7 cells, Klotho increased the expression of both the EpoR protein and mRNA. Klotho also enhanced the transcription activity of the EpoR promoter in H19-7 cells. Moreover, Klotho augmented the Epo-triggered phosphorylation of Jak2 and Stat5 and protected H19-7 cells from hydrogen peroxide cytotoxicity. The silencing of EpoR abolished the protective effect of Klotho against peroxide-induced cytotoxicity. Finally, the silencing of GATA1 diminished the Klotho-induced increase in EpoR protein and mRNA expression as well as its promoter activity. In conclusion, Klotho increased EpoR expression in neuronal cells through GATA1, thereby enabling EpoR to function as a cytoprotective protein against oxidative injury.
机译：促红细胞生成素（Epo）受体（EpoR）在大脑中表达，并在动物模型中显示出对脑损伤的神经保护作用。最近的一项研究表明，EpoR及其活性​​是Klotho在肾脏中进行细胞保护的下游效应器。因此，我们建议Klotho可以刺激神经元细胞中EpoR的表达，以增强Epo介导的保护。用重组Klotho处理H19-7海马神经元细胞。在H19-7细胞中，Klotho增加EpoR蛋白和mRNA的表达。 Klotho还增强了H19-7细胞中EpoR启动子的转录活性。此外，Klotho增强了Epo触发的Jak2和Stat5的磷酸化，并保护H19-7细胞免受过氧化氢的细胞毒性作用。 EpoR的沉默消除了Klotho对过氧化物诱导的细胞毒性的保护作用。最后，GATA1的沉默降低了Klotho诱导的EpoR蛋白和mRNA表达及其启动子活性的增加。总之，Klotho通过GATA1增加了神经元细胞中EpoR的表达，从而使EpoR起到了抗氧化损伤的细胞保护蛋白的作用。

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