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A novel small molecule, LAS-0811, inhibits alcohol-induced apoptosis in VL-17A cells.

Authors
  • Th, Kim
  • Sk, Venugopal
  • M, Zhu
  • Ss, Wang
  • D, Lau
  • Kit S. Lam
  • Dl, Clemens
  • Ma, Zern
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier
Volume
379
Issue
4
Pages
876–881
Identifiers
DOI: 10.1016/j.bbrc.2008.12.133
Source
Kit Lam Lab
License
Unknown

Abstract

One of the pathways by which alcohol induces hepatocyte apoptosis is via oxidative stress. We screened several chemically-synthesized small molecules and found LAS-0811, which inhibits oxidative stress. In this study, we elucidated its role in inhibiting alcohol-induced apoptosis in hepatocyte-like VL-17A cells. VL-17A cells were pre-incubated with LAS-0811, followed by ethanol incubation. Ethanol-induced reactive oxygen species and apoptosis were significantly inhibited in LAS-0811 pre-treated cells. VL-17A cells were transfected with a reporter (ARE/TK-GFP) plasmid containing green fluorescent protein (GFP) as a reporter gene and the anti-oxidant response element as the promoter. LAS-0811 pre-treatment significantly induced the GFP expression compared to the cells treated with ethanol alone. LAS-0811 induced the activation of nrf2 and enhanced the expression and activity of glutathione peroxidase, one of the downstream targets of nrf2. The results indicate that LAS-0811 protects VL-17A cells against ethanol-induced oxidative stress and apoptosis at least in part via nrf2 activation.

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