1. Inhibition of autophagy aggravates molybdenum-induced mitochondrial dysfunction by aggravating oxidative stress in duck renal tubular epithelial cells.
- Author
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Zhuang J, Nie G, Hu R, Wang C, Xing C, Li G, Hu G, Yang F, and Zhang C
- Subjects
- Animals, Antioxidants metabolism, Autophagosomes metabolism, Autophagy drug effects, Catalase metabolism, Ducks metabolism, Ducks physiology, Hydrogen Peroxide metabolism, Membrane Potential, Mitochondrial drug effects, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, Superoxide Dismutase metabolism, Epithelial Cells drug effects, Kidney Tubules drug effects, Mitochondria drug effects, Molybdenum toxicity, Oxidative Stress physiology
- Abstract
Excessive molybdenum (Mo) has adverse effects on animals. To elucidate the effects of autophagy on Mo-induced nephrotoxicity, the duck renal tubular epithelial cells were cultured in medium in absence and presence of (NH
4 )6 Mo7 O24 .4H2 O (0, 480, 720, 960 μM Mo), 3-Methyladenine (3-MA) (2.5 μM), and the combination of Mo and 3-MA for 12 h. After 12 h exposure, the MDC staining, morphologic observation, LC3 puncta, cell viability, autophagy-related genes mRNA and proteins levels, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, antioxidant indices, mitochondrial membrane potential (MMP), mitochondrial mass, mitochondrial respiratory control ratio (RCR) and oxidative phosphorylation rate (OPR) were determined. The results showed that excessive Mo exposure significantly elevated the number of autophagosome and LC3 puncta, upregulated Beclin-1, Atg5, LC3A and LC3B mRNA levels, and LC3II/LC3I and Beclin-1 protein levels, decreased mTOR, p62 and Dynein mRNA levels and p62 protein level. Besides, co-treatment with Mo and 3-MA dramatically increased LDH release, ROS level, hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA) contents as well as cell dam age, reduced cell viability, the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), MMP, mitochondrial mass, mitochondrial RCR and OPR compared to treatment with Mo alone. Taken together, these results suggest that excessive Mo exposure can induce autophagy in duck renal tubular epithelial cells, inhibition of autophagy aggravates Mo-induced mitochondrial dysfunction by regulating oxidative stress., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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