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

Tae Hun Kim, Senthil K. Venugopal, Ming Zhu, Si Si Wang, Derick Lau, Kit S. Lam, Dahn L. Clemens, Mark A. Zern

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)876-881
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume379
Issue number4
DOIs
StatePublished - Feb 20 2009

Keywords

  • Alcohol
  • Liver
  • Nrf2
  • Oxidative stress
  • Small molecule

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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