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Upregulation of Thioredoxin Reductase 1 Expression by Flavan-3-Ols Protects Human Kidney Proximal Tubular Cells from Hypoxia-Induced Cell Death

文献类型： 外文期刊

作者： Zhu, Jixiao 1 ; Fu, Manqin 1 ; Gao, Jian 1 ; Dai, Guoyu 1 ; Guan, Qiunong 1 ; Du, Caigan 1 ;

作者机构： 1.Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada

2.Jiangxi Univ Tradit Chinese Med, Res Ctr Tradit Chinese Med Resources & Ethn Minor, Nanchang 330004, Jiangxi, Peoples R China

3.Guangdong Acad Agr Sci, Sericultural & Agrifood Res Inst, Key Lab Funct Foods, Minist Agr,Guangdong Key Lab Agr Prod Proc, Guangzhou 510610, Peoples R China

关键词： hypoxia; oxidative stress; flavan-3-ols; renal tubular epithelial cells; TXNRD1

期刊名称：ANTIOXIDANTS （ 影响因子：7.675； 五年影响因子：7.886 ）

ISSN：

年卷期： 2022 年 11 卷 7 期

页码：

收录情况： SCI

摘要： Renal hypoxia and its associated oxidative stress is a common pathway for the development of kidney diseases, and using dietary antioxidants such as flavan-3-ols to prevent kidney failure has received much attention. This study investigates the molecular mechanism by which flavan-3-ols prevent hypoxia-induced cell death in renal tubular epithelial cells. Human kidney proximal tubular cells (HKC-8) were exposed to hypoxia (1% O-2) in the presence of flavan-3-ols (catechin, epicatechin, procyanidin B1, and procyanidin B2). Cell death was examined using flow cytometric analysis. Gene expression was determined using a PCR array and Western blotting, and its network and functions were investigated using STRING databases. Here, we show that the cytoprotective activity of catechin was the highest among these flavan-3-ols against hypoxia-induced cell death in cultured HKC-8 cells. Exposure of HKC-8 cells to hypoxia induced oxidative stress leading to up-regulation of DUOX2, NOX4, CYBB and PTGS2 and down-regulation of TXNRD1 and HSP90AA1. Treatment with catechin or other flavan-3-ols prevented the down-regulation of TXNRD1 expression in hypoxic HKC-8 cells. Overexpression of TXNRD1 prevented hypoxia-induced cell death, and inactivation of TXNRD1 with TRi-1, a specific TXNRD1 inhibitor, reduced the catechin cytoprotection against hypoxia-induced HKC-8 cell death. In conclusion, flavan-3-ols prevent hypoxia-induced cell death in human proximal tubular epithelial cells, which might be mediated by their maintenance of TXNRD1 expression, suggesting that enhancing TXNRD1 expression or activity may become a novel therapeutic strategy to prevent hypoxia-induced kidney damage.

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