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Alcohol and Alcoholism Vol. 35, No. 6, pp. 569-573, 2000
© 2000 Medical Council on Alcoholism

ACTIVATION OF NEUTRAL SPHINGOMYELINASE PARTICIPATES IN ETHANOL-INDUCED APOPTOSIS IN HEP G2 CELLS

Jian-Jun Liu, Ji-Yao Wang, Erik Hertervig1, Yajun Cheng2, Åke Nilsson and Rui-Dong Duan2,*

Department of Gastroenterology, Zhongshan Hospital, Shanghai Medical University, Shanghai, People's Republic of China,
1 Department of Internal Medicine and
2 Cell Biology Department 1, Lund University Hospital, S–22185 Lund, Sweden

Received 13 January 2000; first review notified 19 May 2000; accepted 7 June 2000

The mechanism underlying ethanol-induced apoptosis in liver cells is not clear. Sphingomyelin (SM) metabolism is a novel signal transduction pathway that has an impact on apoptosis in many cell types. We investigated whether the SM pathway is involved in ethanol-induced apoptosis in the liver. Hep G2 cells were treated with ethanol followed by assaying apoptosis, sphingomyelinase (SMase) activity, caspase-3 activity, and the changes of SM content in the cells. We found that ethanol dose-dependently increased apoptosis and the effect was accompanied by increases of caspase-3 activity and neutral SMase activity. At concentrations of 80 and 160 mM, ethanol significantly increased caspase-3 activity by 120% and neutral SMase activity by 24%. The activity of acid SMase was only slightly increased without statistical significance. C2-ceramide, the exogenous SM metabolite, mimicked the effects of ethanol on apoptosis and caspase-3 activation. When the SM content was determined 24 h after treatment with ethanol, its level was 15% lower than that of controls. The results indicate that metabolism of SM triggered by neutral SMase participates in ethanol-induced apoptosis in Hep G2 cells and activation of caspase-3 is involved in the apoptotic pathway.


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