From physiological redox signalling to oxidant stress

Jeremy P. T. Ward

doi:10.1007/978-3-319-63245-2_21

From physiological redox signalling to oxidant stress

Jeremy P. T. Ward^*

^*Corresponding author for this work

King's College London

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

18 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 language	English
Title of host publication	Advances in Experimental Medicine and Biology
Publisher	Springer New York LLC
Pages	335-342
Number of pages	8
Volume	967
DOIs	https://doi.org/10.1007/978-3-319-63245-2_21
Publication status	Published - 18 Oct 2017

Publication series

Name	Advances in Experimental Medicine and Biology
Volume	967
ISSN (Print)	00652598
ISSN (Electronic)	22148019

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/978-3-319-63245-2_21

Cite this

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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.",

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PY - 2017/10/18

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N2 - 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.

AB - 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.

KW - Ca signaling

KW - Mitochondria

KW - NADPH oxidases

KW - Pulmonary hypertension

KW - Reactive oxygen species

KW - ROS-induced ROS release

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DO - 10.1007/978-3-319-63245-2_21

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BT - Advances in Experimental Medicine and Biology

PB - Springer New York LLC

ER -

From physiological redox signalling to oxidant stress

Abstract

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Keywords

UN SDGs

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