Ethanol-induced apoptosis in mouse liver

Fas- and cytochrome c-mediated caspase-3 activation pathway

Zhanxiang Zhou, Xiuhua Sun, Yujian Kang

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Hepatic apoptosis has been shown to occur in both experimental and clinical alcoholic liver disease, but the signaling pathway remains unknown. This study was undertaken to examine specifically the involvement of the upstream signals, Fas and cytochrome c, in alcohol-induced caspase-3 activation and apoptosis in the liver. Male FVB mice were administrated intragastrically a single dose of alcohol at 6 g/kg, which has been shown to represent binge drinking in humans. Hepatic apoptosis was detected by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Active form of caspase-3 was identified by immunoperoxidase staining and confirmed by immunogold labeling and was found to be in the cytosol and nucleus. Enzymic assay further confirmed caspase-3 activation and nucleus localization. Systemic administration of caspase-3 inhibitor, Ac-DEVD-FMK, inhibited caspase-3 activity and abrogated apoptosis. Elevation of cytosolic cytochrome c was found by immunoperoxidase staining, immunogold labeling, and Western blot. Increased Fas ligand expression was detected by immunoperoxidase staining. Intravenous administration of a neutralizing Fas ligand monoclonal antibody resulted in suppression of caspase-3 activation and attenuation of apoptosis, but did not inhibit mitochondrial cytochrome c release. The results thus demonstrate that Fas/Fas ligand system-mediated caspase-3 activation plays a central role in the ethanol-induced hepatic apoptosis.

Original languageEnglish (US)
Pages (from-to)329-338
Number of pages10
JournalAmerican Journal of Pathology
Volume159
Issue number1
DOIs
StatePublished - Jan 1 2001

Fingerprint

Cytochromes c
Caspase 3
Ethanol
Apoptosis
Liver
Fas Ligand Protein
Staining and Labeling
Alcohols
Binge Drinking
Alcoholic Liver Diseases
Caspase Inhibitors
DNA Nucleotidylexotransferase
Intravenous Administration
Cytosol
Western Blotting
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Ethanol-induced apoptosis in mouse liver : Fas- and cytochrome c-mediated caspase-3 activation pathway. / Zhou, Zhanxiang; Sun, Xiuhua; Kang, Yujian.

In: American Journal of Pathology, Vol. 159, No. 1, 01.01.2001, p. 329-338.

Research output: Contribution to journalArticle

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