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

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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

Fingerprint

Oxidative stress
Ethanol
Green Fluorescent Proteins
Alcohols
Apoptosis
Molecules
Oxidative Stress
Chemical activation
Antioxidant Response Elements
Hepatocytes
Glutathione Peroxidase
Reactive Oxygen Species
Plasmids
Genes
Cells
Reporter Genes

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, T. H., Venugopal, S. K., Zhu, M., Wang, S. S., Lau, D., Lam, K. S., ... Zern, M. A. (2009). A novel small molecule, LAS-0811, inhibits alcohol-induced apoptosis in VL-17A cells. Biochemical and Biophysical Research Communications, 379(4), 876-881. https://doi.org/10.1016/j.bbrc.2008.12.133

A novel small molecule, LAS-0811, inhibits alcohol-induced apoptosis in VL-17A cells. / Kim, Tae Hun; Venugopal, Senthil K.; Zhu, Ming; Wang, Si Si; Lau, Derick; Lam, Kit S.; Clemens, Dahn L; Zern, Mark A.

In: Biochemical and Biophysical Research Communications, Vol. 379, No. 4, 20.02.2009, p. 876-881.

Research output: Contribution to journalArticle

Kim, Tae Hun ; Venugopal, Senthil K. ; Zhu, Ming ; Wang, Si Si ; Lau, Derick ; Lam, Kit S. ; Clemens, Dahn L ; Zern, Mark A. / A novel small molecule, LAS-0811, inhibits alcohol-induced apoptosis in VL-17A cells. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 379, No. 4. pp. 876-881.
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