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Titolo:
Aldehydes potentiate alpha(2)(I) collagen gene activity by JNK in hepatic stellate cells
Autore:
Anania, FA; Womack, L; Jiang, MD; Saxena, NK;
Indirizzi:
Univ Maryland, Sch Med, Dept Med, Sect Hepatol, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 ect Hepatol, Baltimore, MD 21201 USA Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 nterol, Baltimore, MD 21205 USA
Titolo Testata:
FREE RADICAL BIOLOGY AND MEDICINE
fascicolo: 8, volume: 30, anno: 2001,
pagine: 846 - 857
SICI:
0891-5849(20010415)30:8<846:APACGA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; CULTURED HUMAN-FIBROBLASTS; ALCOHOLIC LIVER-INJURY; GROWTH-FACTOR-BETA; FAT-STORING CELLS; LIPID-PEROXIDATION; OXIDATIVE STRESS; C ACTIVATION; BINDING-SITE; RAT-LIVER;
Keywords:
acetaldehyde; malondialdehyde; stellate cells; collagen; fibrosis; signal transduction; oxidative stress; JNK; free radicals;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Anania, FA Univ Maryland, Med Ctr, 22 S Greene St,Room N3W50, Baltimore, MD 21201 USA Univ Maryland 22 S Greene St,Room N3W50 Baltimore MD USA 21201
Citazione:
F.A. Anania et al., "Aldehydes potentiate alpha(2)(I) collagen gene activity by JNK in hepatic stellate cells", FREE RAD B, 30(8), 2001, pp. 846-857

Abstract

Hepatic stellate cells (HSCs) are responsible for type I collagen deposition in liver fibrosis that leads to cirrhosis. The purpose of this study wasto examine potential molecular signals that lead to increased alpha (2)(I)collagen gene expression by acetaldehyde. the primary metabolite of alcohol and malondialdehyde (MDA), a lipid peroxidation product known to be associated with chronic liver injury. MDA and the combination of MDA and acetaldehyde were employed to determine the effect on alpha (2)(I) collagen gene expression as assessed by transient transfection analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Immunoblot and subsequent immunoprecipitation analysis examined stress-activated protein kinase (SAPK) activity. Cotransfection with a dominant negative mutant for c-jun nuclear kinase (dnJNK1) was also employed with the (YZ(I) collagen promoter. MDA increased alpha (2)(I) collagen gene expression nearly 2.5- to 3-fold, however there was no synergistic effect of the combination of acetaldehyde and MDA on alpha (2)(I) collagen gene activation and expression. Acetaldehyde, MDA, or both significantly increased JNK activity when compared to untreated stellate cells. The dnJNK1 expression vector abrogated alpha (2)(I) collagen transgene activity. In conclusion, JNK activation appears to be critical in the signaling cascade of oxidative metabolites of chronic alcohol-related liver injury and collagen gene activation. (C) 2001 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 09:42:53