Transcriptional responses to oxidative stress: pathological and toxicological implications

Pharmacol Ther. 2010 Mar;125(3):376-93. doi: 10.1016/j.pharmthera.2009.11.004. Epub 2009 Nov 27.


The utilization of molecular oxygen as the terminal electron acceptor for energy production has in many ways shaped the evolution of complex life, physiology, and certain disease processes. The generation of reactive oxygen species (ROS), either as by-products of O(2) metabolism or by specialized enzymes, has the potential to damage cellular components and functions. Exposure to a variety of exogenous toxicants also promotes ROS production directly or through indirect means to cause toxicity. Oxidative stress activates the expression of a wide range of genes that mediate the pathogenic effect of ROS or are required for the detection and detoxification of the oxidants. In many cases, these are mediated by specific transcription factors whose expression, structure, stability, nuclear targeting, or DNA-binding affinity is regulated by the level of oxidative stress. This review examines major transcription factors that mediate transcriptional responses to oxidative stress, focusing on recent progress in the signaling pathways and mechanisms of activation of transcription factors by oxidative stress and the implications of this regulation in the development of disease and chemical toxicity.

Publication types

  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Cardiovascular Diseases / metabolism
  • Gene Expression Regulation*
  • Humans
  • Inflammation / metabolism
  • Metals / adverse effects
  • Models, Biological
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / metabolism
  • Organic Chemicals / adverse effects
  • Oxidative Stress / genetics*
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / adverse effects*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Metals
  • Organic Chemicals
  • Reactive Oxygen Species
  • Transcription Factors