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Titolo:
Inhibition of alcohol dehydrogenase blocks enhanced Gi-protein expression following ethanol treatment in experimental hepatocellular carcinoma in vitro
Autore:
Kovach, SJ; Sitzmann, JV; McKillop, IH;
Indirizzi:
Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 Dept Surg, Rochester, NY 14642 USA
Titolo Testata:
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY
fascicolo: 10, volume: 13, anno: 2001,
pagine: 1209 - 1216
SICI:
0954-691X(200110)13:10<1209:IOADBE>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-GAMMA-SUBUNITS; CYTOCHROME P-4502E1; COUPLED RECEPTORS; ADENYLATE-CYCLASE; HEPATITIS-C; RAT-LIVER; METABOLISM; CIRRHOSIS; KINASE;
Keywords:
acetaldehyde; ethanol; G-proteins; 4-methyl pyrazole; hepatocellular carcinoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: McKillop, IH Univ Rochester, Med Ctr, Dept Surg, Box SURG,601 Elmwood Ave,Rochester, NY 14642 USA Univ Rochester Box SURG,601 Elmwood Ave Rochester NY USA 14642
Citazione:
S.J. Kovach et al., "Inhibition of alcohol dehydrogenase blocks enhanced Gi-protein expression following ethanol treatment in experimental hepatocellular carcinoma in vitro", EUR J GASTR, 13(10), 2001, pp. 1209-1216

Abstract

Objective Chronic alcohol abuse is one of the major contributors to the onset and progression of hepatocellular carcinoma (HCC). We have previously identified increased expression and function of inhibitory guanine nucleotide regulatory proteins (Gi-proteins) in primary human and animal models of HCC. Stimulation of Gi-proteins in HCC stimulates cell mitogenesis, an effect not observed in hepatocytes. The aim of this study was to determine the effect of ethanol and ethanol metabolism on Gi-protein expression in an experimental model of HCC. Design Pharmacological agents that inhibit alcohol metabolism were used inconjunction with ethanol or ethanol metabolites. We were also able to assess the relative contribution of alcohol and acetaldehyde, the major metabolite of alcohol, on Gi-protein expression in HCC and hepatocytes. Methods These studies used the rat hepatic tumorigenic H4IIE cell line in conjunction with isolated rat hepatocytes. Cells were cultured in vitro andexposed to ethanol, ethanol in the presence of an alcohol dehydrogenase (ADH) inhibitor, or acetaldehyde for varying lengths of time. Ethanol metabolism and changes in Gi-protein expression were subsequently determined by assay. Results Exposure to ethanol alone led to significant dose and time dependent increases in Gi alpha1/2 and Gi alpha3 protein and mRNA expression in HCC cells. In contrast, ethanol failed to alter Gi alpha1/2, and only moderately affected Gi alpha3 protein expression in isolated cultured hepatocytes. Pretreatment of HCC cells and hepatocytes with 4-methyl pyrazole (4-MP, 10muM) significantly inhibited alcohol metabolism. Treatment of HCC cells with 4-MP inhibited changes in Gi-protein expression following exposure to ethanol (25 mM, 24 h). In addition, the increased expression of Gi-proteins observed after exposure to ethanol in HCC were mimicked by direct exposure of HCC cells to acetaldehyde in a dose and time dependent manner. Conclusions These data suggest that alcohol metabolites, not alcohol, leadto increased Gi-protein expression in HCC in vitro. Ethanol and ethanol metabolites, in contrast, fail to significantly alter Gi alpha1/2 protein expression in hepatocytes. These data may have significant implications in HCCprogression in vivo. Eur J Gastroenterol Hepatol 13:1209-1216 (C) 2001 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 12:54:58