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Endoplasmic reticulum stress and autophagy contributed to cadmium nephrotoxicity in HK-2 cells and Sprague-Dawley rats

Authors :
Jiaan-Der Wang
Yen-Chuan Ou
Jian-Ri Li
Chun-Jung Chen
Shih-Yi Lin
Chih-Cheng Wu
Wen-Ying Chen
Su-Lan Liao
Ya-Yu Wang
Source :
Food and Chemical Toxicology. 146:111828
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

Excessive accumulation of cadmium is known to cause nephrotoxicity by targeting renal proximal tubular epithelial cells. Studies showed an essential role of autophagy in cadmium-induced nephrotoxicity; however, its underlying mechanisms accompanied by autophagy are incompletely understood. Using an HK-2 human renal proximal tubular epithelial cell line as a study model, sustained exposure of cadmium chloride (CdCl2) was shown to cause cell viability loss, which was alleviated by inhibitors of autophagy but not apoptosis. Data from molecular and biochemical studies revealed an induction of autophagy proteins, intracellular acidic vesicles, and autophagic flux in CdCl2-treated cells. However, there was little sign of apoptosis-related changes. Pharmacological and genetic studies indicated an elevation of Endoplasmic Reticulum (ER) stress, Forkhead Box Class O (FoxO3a), Bcl-2 Interacting Protein 3 (Bnip3), and Beclin1, as well as their involvement in cadmium-induced autophagy and autophagic cell death. Renal injury, histological changes, and molecular marker of ER stress, FoxO3a, Bnip3, and autophagy were observed in the kidney cortex of CdCl2-exposed Sprague-Dawley rats. These observations indicate that ER stress, FoxO3a, Bnip3, and autophagy signaling were actively involved in cadmium-induced nephrotoxicity. Additionally, FoxO3a may act as a linking molecule to convey ER stress signals to Bnip3 and autophagy machinery upon cadmium exposure.

Details

ISSN :
02786915
Volume :
146
Database :
OpenAIRE
Journal :
Food and Chemical Toxicology
Accession number :
edsair.doi.dedup.....1402497f4322fa36b1ee38a19cfb4e61
Full Text :
https://doi.org/10.1016/j.fct.2020.111828