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

38 Citations (Scopus)

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

Fingerprint

Hepatocyte Growth Factor
Metabolism
Hepatocytes
Ethanol
Wounds and Injuries
Oxidative stress
Phosphatidylinositol 3-Kinases
Oxidative Stress
Antioxidants
Glutamate-Cysteine Ligase
Cytochrome P-450 CYP2E1
Glutathione Disulfide
Alcohol Dehydrogenase
Peroxides
Hep G2 Cells
Catalase
Lipid Peroxidation
Cells
Apoptosis
Lipids

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

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

In: Free Radical Biology and Medicine, Vol. 47, No. 4, 15.08.2009, p. 424-430.

Research output: Contribution to journalArticle

Valdés-Arzate, A, Luna, A, Bucio, L, Licona, C, Clemens, DL, Souza, V, Hernandez, E, Kershenobich, D, Gutiérrez-Ruiz, MC & Gómez-Quiroz, LE 2009, 'Hepatocyte growth factor protects hepatocytes against oxidative injury induced by ethanol metabolism', Free Radical Biology and Medicine, vol. 47, no. 4, pp. 424-430. https://doi.org/10.1016/j.freeradbiomed.2009.05.014
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. / Hepatocyte growth factor protects hepatocytes against oxidative injury induced by ethanol metabolism. In: Free Radical Biology and Medicine. 2009 ; Vol. 47, No. 4. pp. 424-430.
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AU - Clemens, Dahn L

AU - Souza, Verónica

AU - Hernandez, Elizabeth

AU - Kershenobich, David

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AU - Gómez-Quiroz, Luis Enrique

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