Pyruvate alleviates high glucose-induced endoplasmic reticulum stress and apoptosis in HK-2 cells.

Xiao Meng Zhang,Fang Qiang Zhou,Xu Chao Ning,Xiu Hong Yang,Hui Min Jin,Jin Dong Tong,Yi Zhen Wang

doi:10.1002/2211-5463.12834

Abstract

Endoplasmic reticulum (ER) stress plays a critical role in the development of diabetic nephropathy (DN). We previously demonstrated that pyruvate (Pyr)‐enriched oral rehydration solution improved glucometabolic disorders and ameliorated DN outcome in db/db mice. Here, we investigated the effects of Pyr on high glucose‐induced ER stress and apoptosis in HK‐2 cells. Our results suggest that high glucose can induce reactive oxygen species production, apoptosis and ER stress in HK‐2 cells, and that Pyr treatment can ameliorate these effects and restore the expression of key proteins involved in ER stress. Thus, Pyr may have potential for the development of novel strategies for the prevention and treatment of clinical DN.

Highlights

Our results suggest that high glucose can induce reactive oxygen species production, apoptosis and Endoplasmic reticulum (ER) stress in HK-2 cells, and that Pyr treatment can ameliorate these effects and restore the expression of key proteins involved in ER stress
ER stress plays a critical role in the progress of diabetes and Abbreviations ATF4, activating transcription factor 4; CCK-8, Cell Counting Kit-8; CHOP, C/EBP homologous protein; CON, control; DMEM, Dulbecco’s modified Eagle’s medium; DN, diabetic nephropathy; ER, endoplasmic reticulum; glucoseregulated protein 78 (GRP78), glucose-regulated protein 78; HG, high glucose; p-EIF2a, phosphorylate a-subunit of eukaryotic initiation factor 2; ROS, reactive oxygen species
Present experiments further explored the protective effect of Pyr on HK-2 cells under the HG condition

Summary

Introduction

Xiao Meng Zhang, Yi Zhen Wang, Jin Dong Tong, Xu Chao Ning, Fang Qiang Zhou4,*, Xiu Hong Yang and Hui Min Jin. Endoplasmic reticulum (ER) stress plays a critical role in the development of diabetic nephropathy (DN). We investigated the effects of Pyr on high glucose-induced ER stress and apoptosis in HK-2 cells. Our results suggest that high glucose can induce reactive oxygen species production, apoptosis and ER stress in HK-2 cells, and that Pyr treatment can ameliorate these effects and restore the expression of key proteins involved in ER stress. ER stress plays a critical role in the progress of diabetes and Abbreviations ATF4, activating transcription factor 4; CCK-8, Cell Counting Kit-8; CHOP, C/EBP homologous protein; CON, control (group); DMEM, Dulbecco’s modified Eagle’s medium; DN, diabetic nephropathy; ER, endoplasmic reticulum; GRP78, glucose-regulated protein 78; HG, high glucose; p-EIF2a, phosphorylate a-subunit of eukaryotic initiation factor 2; ROS, reactive oxygen species.

Methods

Results

Conclusion