期刊
BIOCHIMIE
卷 95, 期 6, 页码 1177-1184出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2013.01.005
关键词
HGF; c-Met; NADPH oxidase; Hepatocytes; ROS
资金
- CONACYT [131707, 233306]
- FUNDHEPA Antonio Ariza Canadilla grant
- Universidad Autonoma Metropolitana-Iztapalapa
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
- Luis E. Gomez-Quiroz (Estancias Sabaticas al Extranjero) [144805]
Redox signaling is emerging as an essential mechanism in the regulation of biological activities of the cell. The HGF/c-Met signaling pathway has been implicated as a key regulator of the cellular redox homeostasis and oxidative stress. We previously demonstrated that genetic deletion of c-Met in hepatocytes disrupts redox homeostasis by a mechanism involving NADPH oxidase. Here, we were focused to address the mechanism of NADPH oxidase regulation by HGF/c-Met signaling in primary mouse hepatocytes and its relevance. HGF induced a biphasic mechanism of NADPH oxidase regulation. The first phase employed the rapid increase in production of ROS as signaling effectors to activate the Nrf2-mediated protective response resulting in up-regulation of the antioxidant proteins, such as NAD(P)H quinone oxidoreductase and gamma-glutamylcysteine synthetase. The second phase operated under a prolonged HGF exposure, caused a suppression of the NADPH oxidase components, including NOX2, NOX4, p22 and p67, and was able to abrogate the TGF beta-induced ROS production and improve cell viability. In conclusion, HGF/c-Met induces a Nrf2-mediated protective response by a double mechanism driven by NADPH oxidase. (C) 2013 Elsevier Masson SAS. All rights reserved.
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