Thioredoxin redox system has been implicated as an intracellular anti-oxidant defense system leading to reduction of cellular oxidative stresses utilizing electrons from NADPH. From high content screening of small molecules targeting the system, gliotoxin, a fungal metabolite, was identified as an active compound. Gliotoxin potently accelerates NADPH oxidation and reduces H2O2. The compound reduces H2O2 to H2O by replacing the function of peroxiredoxin in vitro and decreases intracellular level of H2O2 in HeLa cells. The anti-oxidant activity of gliotoxin was further validated H2O2-mediated cellular phenotype of angiogenesis. The proliferation of endothelial cells was inhibited by the compound at nanomolar range. In addition, H2O2-induced tube formation and invasion of the cells were blocked by gliotoxin. Together, these results demonstrate that gliotoxin is a new small molecule targeting thioredoxin redox system.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 3 Aug 2007|
- Thioredoxin redox system