Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel?

© 2018, Mary Ann Liebert, Inc., publishers. Cellular redox state is a consequence of the balance between the rates of reactive oxygen species and/or reactive nitrogen species, and their dissipation via enzymatic and nonenzymatic redox buffering systems. While low levels of oscillation are associated...

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Main Author: Pervaiz, Shazib
Format: Journal Article
Published: Mary Ann Liebert, Inc. Publishers 2018
Online Access:http://hdl.handle.net/20.500.11937/72234
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author Pervaiz, Shazib
author_facet Pervaiz, Shazib
author_sort Pervaiz, Shazib
building Curtin Institutional Repository
collection Online Access
description © 2018, Mary Ann Liebert, Inc., publishers. Cellular redox state is a consequence of the balance between the rates of reactive oxygen species and/or reactive nitrogen species, and their dissipation via enzymatic and nonenzymatic redox buffering systems. While low levels of oscillation are associated with normal cellular metabolism, stimuli that favor a significant shift in the redox microenvironment, through either the increased production and/or compromise of the antioxidant defenses, induce overt oxidative stress. This change in the redox set point triggers a host of cellular responses ranging from modifications in cellular macromolecules, organelle morphology and physiology, amplified cell-to-cell and intracellular signaling, and changes in genome, epigenome, and proteome. The consequence of this dysregulated cellular homeostasis is therefore manifested in the form of a plethora of pathological states such as inflammation, diabetes mellitus, neurodegenerative disorders, atherosclerosis, and cancer. On the backdrop of these observations, this Forum attempts at reviewing the current understanding of how a prooxidant intracellular milieu favors cell survival while overt oxidative stress results in death execution, and the translation of these biological effects in human disease states, in particular cancer. The far-reaching biochemical, biological, and clinical ramifications of an altered redox environment are also discussed from the standpoint of strategic therapeutic design against refractory and aggressive cancers. It is tempting to conjecture if the inherent or acquired redox heterogeneity, at least in the case of cancer, has evolved as an "evasive mechanism," or presents itself as the "Achilles heel" for therapeutic exploitation.
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spelling curtin-20.500.11937-722342018-12-13T09:34:32Z Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel? Pervaiz, Shazib © 2018, Mary Ann Liebert, Inc., publishers. Cellular redox state is a consequence of the balance between the rates of reactive oxygen species and/or reactive nitrogen species, and their dissipation via enzymatic and nonenzymatic redox buffering systems. While low levels of oscillation are associated with normal cellular metabolism, stimuli that favor a significant shift in the redox microenvironment, through either the increased production and/or compromise of the antioxidant defenses, induce overt oxidative stress. This change in the redox set point triggers a host of cellular responses ranging from modifications in cellular macromolecules, organelle morphology and physiology, amplified cell-to-cell and intracellular signaling, and changes in genome, epigenome, and proteome. The consequence of this dysregulated cellular homeostasis is therefore manifested in the form of a plethora of pathological states such as inflammation, diabetes mellitus, neurodegenerative disorders, atherosclerosis, and cancer. On the backdrop of these observations, this Forum attempts at reviewing the current understanding of how a prooxidant intracellular milieu favors cell survival while overt oxidative stress results in death execution, and the translation of these biological effects in human disease states, in particular cancer. The far-reaching biochemical, biological, and clinical ramifications of an altered redox environment are also discussed from the standpoint of strategic therapeutic design against refractory and aggressive cancers. It is tempting to conjecture if the inherent or acquired redox heterogeneity, at least in the case of cancer, has evolved as an "evasive mechanism," or presents itself as the "Achilles heel" for therapeutic exploitation. 2018 Journal Article http://hdl.handle.net/20.500.11937/72234 10.1089/ars.2018.7586 Mary Ann Liebert, Inc. Publishers restricted
spellingShingle Pervaiz, Shazib
Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel?
title Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel?
title_full Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel?
title_fullStr Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel?
title_full_unstemmed Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel?
title_short Redox Dichotomy in Cell Fate Decision: Evasive Mechanism or Achilles Heel?
title_sort redox dichotomy in cell fate decision: evasive mechanism or achilles heel?
url http://hdl.handle.net/20.500.11937/72234