Epigenetic modifiers exacerbate oxidative stress in renal proximal tubule cells

Edit Nadasi, Jeb S. Clark, Istvan Szanyi, Timea Varjas, I. Ember, Radhakrishna Baliga, Istvan Arany

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Increased production of reactive oxygen species (ROS) by anticancer drugs has been described in patients with various malignancies, which might attribute to their nephrotoxicity. Materials and Methods: The effects of two epigenetic modifiers - trichostatin A (TSA) and 5-aza-deoxycytidine (5AZA) - on ROS production and cell injury alone or in combination with mild oxidative stress were studied in mouse renal proximal tubule cells. Results: Both agents increased mitochondrial ROS production and consequent lactate dehydrogenase (LDH) release either alone or in combination with a low dose of H 2O2. The antioxidant N-acetyl-cysteine (NAC) abolished LDH release. It was also found that CREB-mediated transcription, vital for survival of proximal tubule cells, is attenuated by these anticancer agents. Conclusion: The ROS-inducing activity of TSAI and 5AZA might explain the in vivo nephrotoxicity of epigenetic modifiers. The mechanisms that are responsible for this injury could involve attenuation of pro-survival signaling and/or activation of death signaling pathway(s) associated with mitochondrial ROS release.

Original languageEnglish
Pages (from-to)2295-2299
Number of pages5
JournalAnticancer Research
Volume29
Issue number6
Publication statusPublished - Jun 2009

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Proximal Kidney Tubule
Epigenomics
Reactive Oxygen Species
Oxidative Stress
Deoxycytidine
L-Lactate Dehydrogenase
trichostatin A
Survival
Wounds and Injuries
Antineoplastic Agents
Cysteine
Antioxidants
Pharmaceutical Preparations
Neoplasms

Keywords

  • Cancer
  • Mitochondria
  • Nephrotoxicity
  • ROS
  • Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nadasi, E., Clark, J. S., Szanyi, I., Varjas, T., Ember, I., Baliga, R., & Arany, I. (2009). Epigenetic modifiers exacerbate oxidative stress in renal proximal tubule cells. Anticancer Research, 29(6), 2295-2299.

Epigenetic modifiers exacerbate oxidative stress in renal proximal tubule cells. / Nadasi, Edit; Clark, Jeb S.; Szanyi, Istvan; Varjas, Timea; Ember, I.; Baliga, Radhakrishna; Arany, Istvan.

In: Anticancer Research, Vol. 29, No. 6, 06.2009, p. 2295-2299.

Research output: Contribution to journalArticle

Nadasi, E, Clark, JS, Szanyi, I, Varjas, T, Ember, I, Baliga, R & Arany, I 2009, 'Epigenetic modifiers exacerbate oxidative stress in renal proximal tubule cells', Anticancer Research, vol. 29, no. 6, pp. 2295-2299.
Nadasi E, Clark JS, Szanyi I, Varjas T, Ember I, Baliga R et al. Epigenetic modifiers exacerbate oxidative stress in renal proximal tubule cells. Anticancer Research. 2009 Jun;29(6):2295-2299.
Nadasi, Edit ; Clark, Jeb S. ; Szanyi, Istvan ; Varjas, Timea ; Ember, I. ; Baliga, Radhakrishna ; Arany, Istvan. / Epigenetic modifiers exacerbate oxidative stress in renal proximal tubule cells. In: Anticancer Research. 2009 ; Vol. 29, No. 6. pp. 2295-2299.
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