Epigenetic modifiers exert renal toxicity through induction of p66shc

Istvan Arany, Jeb S. Clark, I. Ember, Luis A. Juncos

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3267-3271
Number of pages5
JournalAnticancer Research
Volume31
Issue number10
Publication statusPublished - Oct 2011

Fingerprint

trichostatin A
Azacitidine
Epigenomics
Cytochromes c
Kidney
Reactive Oxygen Species
Proximal Kidney Tubule
Wounds and Injuries
Binding Sites
Mutation

Keywords

  • Epigenetic modifiers
  • Kidney
  • Mitochondria
  • P66shc
  • ROS
  • Toxicity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Arany, I., Clark, J. S., Ember, I., & Juncos, L. A. (2011). Epigenetic modifiers exert renal toxicity through induction of p66shc. Anticancer Research, 31(10), 3267-3271.

Epigenetic modifiers exert renal toxicity through induction of p66shc. / Arany, Istvan; Clark, Jeb S.; Ember, I.; Juncos, Luis A.

In: Anticancer Research, Vol. 31, No. 10, 10.2011, p. 3267-3271.

Research output: Contribution to journalArticle

Arany, I, Clark, JS, Ember, I & Juncos, LA 2011, 'Epigenetic modifiers exert renal toxicity through induction of p66shc', Anticancer Research, vol. 31, no. 10, pp. 3267-3271.
Arany, Istvan ; Clark, Jeb S. ; Ember, I. ; Juncos, Luis A. / Epigenetic modifiers exert renal toxicity through induction of p66shc. In: Anticancer Research. 2011 ; Vol. 31, No. 10. pp. 3267-3271.
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