TY - JOUR
T1 - Hepatocyte growth factor protects hepatocytes against oxidative injury induced by ethanol metabolism
AU - Valdés-Arzate, Argelia
AU - Luna, Armando
AU - Bucio, Leticia
AU - Licona, Cynthia
AU - Clemens, Dahn L.
AU - Souza, Verónica
AU - Hernandez, Elizabeth
AU - Kershenobich, David
AU - Gutiérrez-Ruiz, María Concepción
AU - Gómez-Quiroz, Luis Enrique
N1 - Funding Information:
This work was partially funded by grants from the Consejo Nacional de Ciencia y Tecnología (CONACYT 61544 and 45921); by FUNDHEPA and FUNSALUD grants from Antonio Ariza Cañadilla, Secretaría de Educación Pública (PIFI2006-35-129-346/CA 142006-35-40); and by the Universidad Autónoma Metropolitana–Iztapalapa. We thank CONACYT for financial support to Argelia Valdés-Arzate for her Ph.D. studies. We also thank Snorri S. Thorgeirsson and Valentina Factor, from the National Cancer Institute, National Institutes of Health, USA, for invaluable guidance in the field of c-Met/HGF.
PY - 2009/8/15
Y1 - 2009/8/15
N2 - 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.
AB - 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.
KW - Alcoholic liver disease
KW - Cytochrome P450 2E1
KW - Ethanol
KW - Free radicals
KW - HepG2
KW - Oxidative stress
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U2 - 10.1016/j.freeradbiomed.2009.05.014
DO - 10.1016/j.freeradbiomed.2009.05.014
M3 - Article
C2 - 19463946
AN - SCOPUS:67650034524
VL - 47
SP - 424
EP - 430
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 4
ER -