From physiological redox signalling to oxidant stress

Jeremy P. T. Ward*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

16 Citations (Scopus)

Abstract

Oxidant stress is strongly associated with cardiovascular disease, including pulmonary hypertension, but antioxidant therapies have so far proven ineffective. This is partly due to a lack of understanding of the key role played by reactive oxygen species (ROS) in physiological cell signalling, and partly to the complex interrelationships between generators of ROS (e.g. mitochondria and NADPH oxidases, NOX), cellular antioxidant systems and indeed Ca2+ signalling. At physiological levels ROS reversibly affect the function of numerous enzymes and transcription factors, most often via oxidation of specific protein thiols. Importantly, they also affect pathways that promote ROS generation by NOX or mitochondria (ROS-induced ROS release), which has an inherent propensity for positive feedback and uncontrolled oxidant production. The reason this does not occur under normal conditions reflects in part a high level of compartmentalisation of ROS signalling within the cell, akin to that for Ca2+. This article considers the physiological processes which regulate NOX and mitochondrial ROS production and degradation and their interactions with each other and Ca2+ signalling pathways, and discusses how loss of spatiotemporal constraints and activation of positive feedback pathways may impact on their dysregulation in pulmonary hypertension.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages335-342
Number of pages8
Volume967
DOIs
Publication statusPublished - 18 Oct 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume967
ISSN (Print)00652598
ISSN (Electronic)22148019

Keywords

  • Ca signaling
  • Mitochondria
  • NADPH oxidases
  • Pulmonary hypertension
  • Reactive oxygen species
  • ROS-induced ROS release

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