Antioxidant responses and cellular adjustments to oxidative stress

Redox Biol. 2015 Dec;6:183-197. doi: 10.1016/j.redox.2015.07.008. Epub 2015 Jul 21.

Abstract

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases.

Keywords: Antioxidants; ER stress; Ischemia–reperfusion; Redox signaling; Transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Antioxidants / metabolism
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / pathology
  • Endoplasmic Reticulum Stress / genetics*
  • Gene Expression Regulation
  • Glutathione / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Peroxiredoxins / genetics
  • Peroxiredoxins / metabolism
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Signal Transduction
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism

Substances

  • Antioxidants
  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Transcription Factor AP-1
  • Peroxiredoxins
  • Glutathione