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Updated: May 28, 2026

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes
Published on: January 16, 2015
Epigenetic modifiers exert renal toxicity through induction of p66shc
Istvan Arany1, Jeb S Clark, Istvan Ember
1Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, U.S.A. iarany@umc.edu
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(2)O(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.
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