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

作者：Kim Tae Hun; Venugopal Senthil K; Zhu Ming; Wang Si Si; Lau Derick; Lam Kit S; Clemens Dahn L; Zern Mark A^*

来源：Biochemical and Biophysical Research Communications, 2009, 379(4): 876-881.

DOI：10.1016/j.bbrc.2008.12.133

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

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.

• 出版日期2009-2-20
• 单位吉林大学