ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium-induced ROS in mouse spermatocytes. (December 2017)

• Record Type: Journal Article
• Authors: Li, Renyan; Luo, Xue; Zhu, Yijian; Zhao, Letian; Li, Lianbing; Peng, Qiang; Ma, Mingfu; Gao, Yanfei
• Is Part Of: Environmental pollution. Volume 231:Part 2(2017)
• Page Start: 1560
• Page End: 1568
• Publication Date: 2017-12
• Subjects: Cadmium -- Melatonin -- Oxidative stress -- DNA damage -- Autophagy; Cd Cadmium -- CdCl2 Cadmium chloride -- AMPK AMP-activated protein kinase -- ROS Reactive oxygen species -- ATM Ataxia telangiectasia mutated -- DSBs Double-strand breaks -- TEM Transmission electron microscopy -- ELISA Enzyme linked immunospecific assay; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2017.09.044
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the exact mechanism and role of autophagy induced by Cd in spermatozoa cells. Mouse spermatocyte-derived cells (GC-2) were treated with 20 μM Cd chloride for 24 h. The level of reactive oxygen species (ROS), DNA damage, autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase (AMPK)/mTOR were determined. The results showed that Cd induced autophagy and DNA damage in GC-2 cells via ROS generation, and the autophagy signal pathway AMPK/mTOR was activated by ATM which is a DNA damage sensor. Melatonin, a well-known antioxidant, ameliorated DNA damage, and inhibited autophagy via the AMPK/mTOR signal pathway. Furthermore, after inhibition of autophagy by knockdown of AMPKα, increased DNA damage by Cd treatment was observed in GC-2 cells. These findings demonstrated the protective role of autophagy in DNA damage and suggested that the mechanism of autophagy induced by Cd was through the ATM/AMPK/mTOR signal pathway in spermatozoa cells. Graphical abstract: Highlights: Intracellular ROS was involved in Cd induced autophagy. DNA damage was involved in Cd induced autophagy. AMPK/mTOR activation was involved in Cd induced autophagy. Inhibition of autophagy by knockdown AMPKα was involved in Cd increased DNA damage. Melatonin suppressed Cd induced autophagy through inhibition of DNA damage in testis of mice.