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

Argelia Valdés-Arzate, Armando Luna, Leticia Bucio, Cynthia Licona, Dahn L. Clemens, Verónica Souza, Elizabeth Hernandez, David Kershenobich, María Concepción Gutiérrez-Ruiz, Luis Enrique Gómez-Quiroz

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)424-430
Number of pages7
JournalFree Radical Biology and Medicine
Volume47
Issue number4
DOIs
StatePublished - Aug 15 2009

Keywords

  • Alcoholic liver disease
  • Cytochrome P450 2E1
  • Ethanol
  • Free radicals
  • HepG2
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Valdés-Arzate, A., Luna, A., Bucio, L., Licona, C., Clemens, D. L., Souza, V., Hernandez, E., Kershenobich, D., Gutiérrez-Ruiz, M. C., & Gómez-Quiroz, L. E. (2009). Hepatocyte growth factor protects hepatocytes against oxidative injury induced by ethanol metabolism. Free Radical Biology and Medicine, 47(4), 424-430. https://doi.org/10.1016/j.freeradbiomed.2009.05.014