title: Biphasic regulation of the NADPH oxidase by HGF/c-Met signaling pathway in primary mouse hepatocytes.
abstract: 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 γ-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 TGFβ-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.
authors: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina S-351, 09340 Iztapalapa, México, D.F., Mexico; PhD program on Experimental Biology, Universidad Autónoma Metropolitana Iztapalapa, México, D.F., Mexico.
authors: Denise
authors: D
authors: Clavijo-Cornejo
authors: Cristina
authors: C
authors: Enriquez-Cortina
authors: Alberto
authors: A
authors: López-Reyes
authors: Mayra
authors: M
authors: Domínguez-Pérez
authors: Natalia
authors: N
authors: Nuño
authors: Marcela
authors: M
authors: Domínguez-Meraz
authors: Leticia
authors: L
authors: Bucio
authors: Verónica
authors: V
authors: Souza
authors: Valentina M
authors: VM
authors: Factor
authors: Snorri S
authors: SS
authors: Thorgeirsson
authors: María Concepción
authors: MC
authors: Gutiérrez-Ruiz
authors: Luis E
authors: LE
authors: Gómez-Quiroz
mesh_terms: D000818:Animals; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C553307:HGF protein, mouse; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D017228:Hepatocyte Growth Factor; D019255:NADPH Oxidases; D019859:Proto-Oncogene Proteins c-met