Back to Search
Start Over
Endoplasmic reticulum stress and autophagy contributed to cadmium nephrotoxicity in HK-2 cells and Sprague-Dawley rats
- 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.
- Subjects :
- Male
inorganic chemicals
Programmed cell death
Cell Survival
Cadmium chloride
Toxicology
Cell Line
Nephrotoxicity
Kidney Tubules, Proximal
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0404 agricultural biotechnology
Autophagy
Animals
Humans
030304 developmental biology
0303 health sciences
Endoplasmic reticulum
Forkhead Box Protein O3
Epithelial Cells
04 agricultural and veterinary sciences
General Medicine
Endoplasmic Reticulum Stress
040401 food science
Rats
Cell biology
Gene Expression Regulation
chemistry
Apoptosis
Unfolded protein response
Kidney Diseases
Intracellular
Cadmium
Food Science
Subjects
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