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Overexpression of augmenter of liver regeneration (ALR) mitigates the effect of H2O2-induced endoplasmic reticulum stress in renal tubule epithelial cells

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Abstract

Ischemia/reperfusion is a major cause of acute kidney injury and can induce apoptosis in renal epithelial tubule (HK-2) cells. Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a major contributor to apoptosis in acute kidney injury. We previously reported that augmenter of liver regeneration (ALR) functions as an anti-apoptotic factor in H2O2-treated HK-2 cells although the precise mechanism underlying this action remains unclear. In the present study, we investigate the role of ALR in H2O2-induced ER stress-mediated apoptosis. We overexpressed ALR and established a H2O2-induced ER stress model in HK-2 cells. Overexpression of ALR reduced the level of reactive oxygen species and the rate of apoptosis in H2O2-treated HK-2 cells. Using confocal microscopy and western blot, we observed that ALR colocalized with the ER and mitochondria compartment. Moreover, ALR suppressed ER stress by maintaining the morphology of the ER and reducing the levels of the ER-related proteins, glucose-regulated protein 78 (GRP78), phospho-protein kinase-like ER kinase (p-PERK), phospho-eukaryotic initiation factor 2α (p-eIF2α) and C/EBP-homologous protein (CHOP) significantly (p < 0.05). Mechanistically, ALR promoted Bcl-2 expression and suppressed Bax and cleaved-caspase-3 expression significantly during ER-stress induced apoptosis (p < 0.05). Furthermore, ALR attenuated calcium release from the ER, and transfer to mitochondria, under ER stress. To conclude, ALR alleviates H2O2-induced ER stress-mediated apoptosis in HK-2 cells by suppressing ER stress response and by maintaining calcium homeostasis. Consequently, ALR may protect renal tubule epithelial cells from ischemia/reperfusion induced acute kidney injury.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81873604 and 30971334), Natural Science Foundation Project of CQ CSTC (Grant No. cstc2015jcyjA10069), Medical Scientific Research Projects of Chongqing Health and Family Planning Commission (Grant No. 20142031) and The Found for Fostering Talents in Scientific Research of Chongqing Medical University (Grant No. 201404).

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Authors and Affiliations

  1. Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Xiao Jiang, Xiao-hui Liao, Li-li Huang & Ling Zhang

  2. Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Hang Sun & Qi Liu

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Jiang, X., Liao, Xh., Huang, Ll. et al. Overexpression of augmenter of liver regeneration (ALR) mitigates the effect of H2O2-induced endoplasmic reticulum stress in renal tubule epithelial cells. Apoptosis 24, 278–289 (2019). https://doi.org/10.1007/s10495-019-01517-z

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