Hepatocyte growth factor protects hepatocytes against oxidative injury induced by ethanol metabolism

• Published in: Free radical biology & medicine Vol. 47; no. 4; pp. 424 - 430
• Main Authors: Valdés-Arzate, Argelia, Luna, Armando, Bucio, Leticia, Licona, Cynthia, Clemens, Dahn L., Souza, Verónica, Hernandez, Elizabeth, Kershenobich, David, Gutiérrez-Ruiz, María Concepción, Gómez-Quiroz, Luis Enrique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2009
• Subjects: 1-Phosphatidylinositol 3-kinase; Alcoholic liver disease; Androstadienes - pharmacology; Catalase - genetics; Catalase - metabolism; Cell Extracts; Cell Line; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450 2E1; Cytochrome P450 Family 2; Cytoprotection; Ethanol; Ethanol - metabolism; Free radicals; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - genetics; Glutamate-Cysteine Ligase - genetics; Glutamate-Cysteine Ligase - metabolism; Glutathione - metabolism; Hepatocyte Growth Factor - metabolism; Hepatocyte Growth Factor - therapeutic use; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; HepG2; Humans; Lipid Peroxidation - drug effects; Lipid Peroxidation - genetics; Liver Diseases, Alcoholic - drug therapy; Neurophysins - genetics; NF-kappa B - antagonists & inhibitors; Oxidative Stress; Peptides - pharmacology; Protein Precursors - genetics; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Signal Transduction - drug effects; Signal Transduction - genetics; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Transfection; Transgenes - genetics; Vasopressins - genetics; HepG2; Oxidative stress; Free radicals; Ethanol; Cytochrome P450 2E1; Alcoholic liver disease
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2009.05.014

Hepatocyte growth factor (HGF) is involved in many cellular responses, such as mitogenesis and apoptosis protection; however, its effect against oxidative injury induced by ethanol metabolism is not well understood. The aim of this work was to address the mechanism of HGF-induced protection against ethanol-generated oxidative stress damage in the human cell line VL-17A (cytochrome P450 2E1/alcohol dehydrogenase-transfected HepG2 cells). Cells were pretreated with 50 ng/ml HGF for 12 h and then treated with 100 mM ethanol for 0–48 h. Some parameters of oxidative damage were evaluated. We found that ethanol induced peroxide formation (3.3-fold) and oxidative damage as judged by lipid peroxidation (5.4-fold). Damage was prevented by HGF. To address the mechanisms of HGF-induced protection we investigated the cellular antioxidant system. We found that HGF increased the GSH/GSSG ratio, as well as SOD1, catalase, and γ-glutamylcysteine synthetase expression. To explore the signaling pathways involved in this process, VL-17A cells were pretreated with inhibitors against PI3K, Akt, and NF-κB. We found that all treatments decreased the expression of the antioxidant enzymes, thus abrogating the HGF-induced protection against oxidative stress. Our results demonstrate that HGF protects cells from the oxidative damage induced by ethanol metabolism by a mechanism driven by NF-κB and PI3K/Akt signaling.