Background/Aims: Trichostatin A (TSA) and 5-azacytidine (5AZA) induce reactive oxygen species (ROS)-mediated injury in renal proximal tubule cells. Since TSA and 5AZA are activators of p66shc, we questioned whether p66shc may mediate renal toxicity of TSA- and 5AZA. Materials and Methods: Renal proximal tubule cells were treated with either TSA or 5AZA for 24 hours followed by treatment with 200 μM H 2O 2. Expression of p66shc and activity of its promoter, as well as its mitochondrial and cytochrome c binding were determined. Impact of knockdown of p66shc and mutation of its cytochrome c-binding site on ROS production and cell injury was studied. Results: TSA, and 5AZA increased expression of p66shc through induction of its promoter and also increased its mitochondrial/cytochrome c binding. Knockdown or mutation of the cytochrome c binding site of p66shc attenuated ROS production and cell injury. Conclusion: Therapeutic means that interfere with induction of p66shc may ameliorate renal toxicity of those epigenetic modifiers.
|Number of pages||5|
|Publication status||Published - okt. 1 2011|
ASJC Scopus subject areas
- Cancer Research