Endoplasmic Reticulum Stress-Activated PERK-eIF2 alpha-ATF4 Signaling Pathway is Involved in the Ameliorative Effects of Ginseng Polysaccharides against Cisplatin-Induced Nephrotoxicity in Mice

文献类型： 外文期刊

第一作者： Wei, Xiao-Meng

作者： Wei, Xiao-Meng;Jiang, Shuang;Wang, Shi-Han;Liu, Wen-Cong;Wang, Zi;Wang, Ying-Ping;Zhang, Rui;Li, Wei;Jiang, Shuang;Wang, Shi-Han;Liu, Wen-Cong;Wang, Zi;Wang, Ying-Ping;Zhang, Rui;Li, Wei;Li, Shan-Shan;Sun, Yin-Shi

作者机构：

期刊名称：ACS OMEGA （ 影响因子：2.87； 五年影响因子：2.905 ）

ISSN： 2470-1343

年卷期： 2021 年 6 卷 13 期

页码：

收录情况： SCI

摘要： Although previous studies have reported that saponins (ginsenosides, the major active and most representative ingredients in Panax ginseng C.A. Meyer) exerted a good ameliorative effect on cisplatin (CP)-induced acute kidney injury in animal models, little attention has been paid to a large number of polysaccharides isolated and purified from ginseng. This work aimed to investigate the protective effect and the possible molecular mechanism of ginseng polysaccharide (WGP) on CP-induced kidney toxicology in mice. The results from biomarker analysis including serum creatinine (CRE) and blood urea nitrogen (BUN) confirmed the protective effect of WGP at 200 and 400 mg/kg on CP-induced renal-toxicology. We found that WGP reduces the apoptosis of kidney cells by inhibiting endoplasmic reticulum (ER) stress caused by CP, which is manifested by increased phosphorylation of PERK. In addition, the apoptosis-associated with caspase 3 activation in renal cells induced by CP was inhibited after administration of WGP, and the phosphorylation levels of PI3K and AKT were also reduced significantly. We also demonstrated that after exposure to CP, the unfolded protein response signaling pathway PERK-eIF2 alpha-ATF4 axis was significantly activated, manifested by increased phosphorylation of eIF2 alpha and increased expression of ATF4 and CHOP. Interestingly, the WGP administration improves this situation. Furthermore, the supplement of WGP inhibited the overexpression of nuclear factor-kappa B p65 (NF-kappa B p65) and tumor necrosis factor-alpha (TNF-alpha) caused by CP exposure. In short, for the first time, our findings indicated that WGP could effectively prevent CP-induced ER stress, inflammation, and apoptosis in renal cells, in part, by regulating the PI3K/AKT and PERK-eIF2 alpha-ATF4 signaling pathways.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序