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Zinc transporter 5 and zinc transporter 7 induced by high glucose protects peritoneal mesothelial cells from undergoing apoptosis

机译:高糖诱导的锌转运蛋白5和锌转运蛋白7保护腹膜间皮细胞免于凋亡

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摘要

Zinc is an essential micronutrient and cytoprotectant involved in many types of apoptosis. The zinc transporter family SLC30A (ZnTs) is an important factor in the regulation of zinc homeostasis; however, its function in apoptosis in peritoneal mesothelial cells (PMCs) remains unknown. This study explores the regulation of zinc transporters and how they play a role in cell survival, particularly in rat peritoneal mesothelial cells (RPMCs), surrounding glucose concentrations, and the molecular mechanism involved. The messenger RNA (mRNA) transcripts were quantitatively measured by real-time polymerase chain reaction for all known nine zinc transport exporters (SLC30A1-8,. 10), as well as in primary RPMCs and the cells cultured under nonstimulated and HG-stimulated conditions. While many zinc transporters were constitutively expressed, ZnT5 mRNA and ZnT7 mRNA were strongly induced by HG. Overexpression of ZnT5 and ZnT7 respectively resulted in a decrease in the expression of caspace 3, caspace 8, BAX, and AIF and coincided with cell survival in the presence of HG. Inhibition of ZnT5 and ZnT7 expression using considerable siRNA-mediated knockdown of RPMCs was examined and, afterwards, the impact on cell apoptosis was investigated. Increased levels of apoptosis were observed after knockdown of ZnT5 and ZnT7. Furthermore, overexpression of ZnT5 and ZnT7 is accompanied by activation of PI3K/Akt pathway and inhibiting HG-induced apoptosis. This study suggests that the zinc transporting system in RPMCs is influenced by exposure to HG, particularly ZnT5 and ZnT7. This may account for the inhibition of HG-induced RPMC apoptosis and peritoneum injury, likely through targeting PI3K/Akt pathway-mediated cell survival.
机译:锌是参与多种类型细胞凋亡的必需微量营养素和细胞保护剂。锌转运蛋白家族SLC30A(ZnTs)是调节锌稳态的重要因素。然而,其在腹膜间皮细胞(PMCs)凋亡中的功能仍然未知。这项研究探讨了锌转运蛋白的调控及其在细胞存活中的作用,特别是在大鼠腹膜间皮细胞(RPMC),周围的葡萄糖浓度以及涉及的分子机制中。通过实时聚合酶链反应对所有已知的九种锌转运输出蛋白(SLC30A1-8,.10)以及初级RPMC和在非刺激和HG刺激条件下培养的细胞进行实时聚合酶链反应定量测量信使RNA(mRNA)转录本。尽管许多锌转运蛋白被组成型表达,但HG强烈诱导ZnT5 mRNA和ZnT7 mRNA。 ZnT5和ZnT7的过表达分别导致caspace 3,caspace 8,BAX和AIF的表达下降,并且与存在HG时的细胞存活率一致。研究了使用大量siRNA介导的RPMC敲低来抑制ZnT5和ZnT7的表达,然后研究了对细胞凋亡的影响。敲低ZnT5和ZnT7后,观察到凋亡水平增加。此外,ZnT5和ZnT7的过表达伴随着PI3K / Akt途径的激活和抑制HG诱导的细胞凋亡。这项研究表明,RPMC中的锌转运系统受暴露于HG(尤其是ZnT5和ZnT7)的影响。这可能是通过靶向PI3K / Akt途径介导的细胞存活来抑制HG诱导的RPMC凋亡和腹膜损伤。

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