Reactive oxygen species in cell signaling

doi:10.1152/AJPLUNG.2000.279.6.L1005

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Reactive oxygen species in cell signaling

Journal Article•DOI•

Reactive oxygen species in cell signaling

Victor J. Thannickal¹, Barry L. Fanburg¹•Institutions (1)

01 Dec 2000-American Journal of Physiology-lung Cellular and Molecular Physiology (American Physiological Society)-Vol. 279, Iss: 6

TL;DR: The evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated is examined.

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Abstract: Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When cellular production of ROS overwhelms its antioxidant capacity, damage to cellular macromolecules such as lipids, protein, and DNA may ensue. Such a state of “oxidative stress” is thought to contribute to the pathogenesis of a number of human diseases including those of the lung. Recent studies have also implicated ROS that are generated by specialized plasma membrane oxidases in normal physiological signaling by growth factors and cytokines. In this review, we examine the evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated. Emerging concepts on the mechanisms of signal transduction by ROS that involve alterations in cellular redox state and oxidative modifications of proteins are also discussed.

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Journal Article•DOI•

Free radicals and antioxidants in normal physiological functions and human disease

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Marian Valko, Dieter Leibfritz¹, Ján Moncol, Mark T. D. Cronin², Milan Mazúr, Joshua Telser³ - Show less +2 more•Institutions (3)

University of Bremen¹, Liverpool John Moores University², Roosevelt University³

01 Jan 2007-The International Journal of Biochemistry & Cell Biology

TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

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12,240 citations

Cites background from "Reactive oxygen species in cell sig..."

...Signal transduction is triggered by extracellular signals such as hormones, growth factors, cytokines and neurotransmitters (Thannickal & Fanburg, 2000)....
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...…3 (IL-3), tumor ecrosis factor- (TNF- ), angiotensin II (ANGII), latelet derived growth factor (PDGF), nerve growth actor (NGF), transforming growth factor- 1 (TGF1), granulocyte-macrophage colony-stimulating facor (GM-CSF), and fibroblast growth factor (FGF-2) Thannickal & Fanburg, 2000)....
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...Both of these “redox buffering” thiol systems counteract intracellular oxidative stress; in addition to antioxidant functioning in the cell, GSH and TRX are involved in cell signalling process (Dröge, 2002; Thannickal & Fanburg, 2000)....
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...Most cell types have been shown to elicit a mall oxidative burst generating low concentrations f ROS when they are stimulated by cytokines, rowth factors and hormones, e.g. interleukin-1 (IL), interleukin 6 (IL-6), interleukin 3 (IL-3), tumor ecrosis factor- (TNF- ), angiotensin II (ANGII), latelet derived growth factor (PDGF), nerve growth actor (NGF), transforming growth factor- 1 (TGF1), granulocyte-macrophage colony-stimulating facor (GM-CSF), and fibroblast growth factor (FGF-2) Thannickal & Fanburg, 2000)....
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...These signal transduction processes can induce various biological activities, such as muscle con- of Bioc t m c s ( c R o a s o g 1 n p f t ( t e R l p M. Valko et al. / The International Journal raction, gene expression, cell growth, and nerve transission (Thannickal & Fanburg, 2000)....
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Journal Article•DOI•

Free radicals, metals and antioxidants in oxidative stress-induced cancer

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Marian Valko, Christopher J. Rhodes¹, Ján Moncol, Mario Izakovic, Milan Mazúr - Show less +1 more•Institutions (1)

University of Reading¹

10 Mar 2006-Chemico-Biological Interactions

TL;DR: This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process and the role of enzymatic and non-enzymatic antioxidants in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors.

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5,937 citations

Journal Article•DOI•

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

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Karen Bedard¹, Karl-Heinz Krause•Institutions (1)

University of Geneva¹

01 Jan 2007-Physiological Reviews

TL;DR: This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.

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Abstract: For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

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5,873 citations

Journal Article•DOI•

Reactive Oxygen Species in Inflammation and Tissue Injury

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Manish Mittal¹, Mohammad Rizwan Siddiqui¹, Khiem Tran¹, Sekhar P. Reddy¹, Asrar B. Malik - Show less +1 more•Institutions (1)

University of Illinois at Chicago¹

01 Mar 2014-Antioxidants & Redox Signaling

TL;DR: The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.

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Abstract: Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.

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2,813 citations

Cites background from "Reactive oxygen species in cell sig..."

...OH is defined as the most potent oxidizing species of biological membrane proteins and lipids and has an extremely short half life (150, 374, 413)....
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...Although others may be important in signaling and disease (155, 413), their functions remain poorly understood....
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...At ‘‘physiological concentrations,’’ ROS function as signaling molecules that regulate cell growth, the adhesion of cells toward other cells, differentiation, senescence, and apoptosis (102, 413)....
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...What are the biologically relevant ROS? The widely studied and understood family members are the superoxide anion (O2 (2)), hydroxyl radical (OH ), hydrogen peroxide (H2O2), and hypochlorous acid (HOCl) (413)....
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Journal Article•DOI•

Reactive oxygen species, antioxidants, and the mammalian thioredoxin system.

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Jonas Nordberg¹, Elias S.J. Arnér¹•Institutions (1)

Karolinska Institutet¹

01 Dec 2001-Free Radical Biology and Medicine

TL;DR: The TrxR-catalyzed regeneration of several antioxidant compounds, including ascorbic acid (vitamin C), selenium-containing substances, lipoic acid, and ubiquinone are summarized.

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2,632 citations

Cites background from "Reactive oxygen species in cell sig..."

...Enzymes similar to components of this complex are also present in nonphagocytic cells where their functions should be connected to signaling [14]....
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...Several cytokines, growth factors, hormones, and neurotransmitters use ROS as secondary messengers in the intracellular signal transduction [14]....
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References

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Book•

Free radicals in biology and medicine

[...]

Barry Halliwell, John M.C. Gutteridge

13 Jun 1985

TL;DR: 1. Oxygen is a toxic gas - an introduction to oxygen toxicity and reactive species, and the chemistry of free radicals and related 'reactive species'

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Abstract: 1. Oxygen is a toxic gas - an introductionto oxygen toxicity and reactive species 2. The chemistry of free radicals and related 'reactive species' 3. Antioxidant defences Endogenous and Diet Derived 4. Cellular responses to oxidative stress: adaptation, damage, repair, senescence and death 5. Measurement of reactive species 6. Reactive species can pose special problems needing special solutions. Some examples. 7. Reactive species can be useful some more examples 8. Reactive species can be poisonous: their role in toxicology 9. Reactive species and disease: fact, fiction or filibuster? 10. Ageing, nutrition, disease, and therapy: A role for antioxidants?

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21,528 citations

"Reactive oxygen species in cell sig..." refers background in this paper

...It has been postulated that electron “leaks” from these enzymatic systems may give rise to ROS that can damage cellular DNA in vivo (102)....
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...A free radical is defined as any atomic or molecular species capable of independent existence that contains one or more unpaired electrons in one of its molecular orbitals (102)....
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...Nuclear membranes contain cytochrome oxidases and electron transport systems that resemble those of the ER but the function of which is unknown (78, 102)....
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Journal Article•DOI•

Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

[...]

Richard M.J. Palmer, A. G. Ferrige, Salvador Moncada

01 Jun 1987-Nature

TL;DR: NO released from endothelial cells is indistinguishable from EDRF in terms of biological activity, stability, and susceptibility to an inhibitor and to a potentiator.

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Abstract: Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which mediates the action of some vasodilators. Nitrovasodilators, which may act by releasing nitric oxide (NO), mimic the effect of EDRF and it has recently been suggested by Furchgott that EDRF may be NO. We have examined this suggestion by studying the release of EDRF and NO from endothelial cells in culture. No was determined as the chemiluminescent product of its reaction with ozone. The biological activity of EDRF and of NO was measured by bioassay. The relaxation of the bioassay tissues induced by EDRF was indistinguishable from that induced by NO. Both substances were equally unstable. Bradykinin caused concentration-dependent release of NO from the cells in amounts sufficient to account for the biological activity of EDRF. The relaxations induced by EDRF and NO were inhibited by haemoglobin and enhanced by superoxide dismutase to a similar degree. Thus NO released from endothelial cells is indistinguishable from EDRF in terms of biological activity, stability, and susceptibility to an inhibitor and to a potentiator. We suggest that EDRF and NO are identical.

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10,739 citations

Journal Article•DOI•

Hydroperoxide metabolism in mammalian organs.

[...]

Britton Chance, Helmut Sies, Alberto Boveris

01 Jul 1979-Physiological Reviews

5,682 citations

"Reactive oxygen species in cell sig..." refers background in this paper

...Thus unlike H2O2, which is capable of diffusing across the mitochondrial membrane into the cytoplasm (44), mitochondria-generated O2 (2)z is unlikely to escape into the cytoplasm....
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Journal Article•DOI•

Nitric oxide as a secretory product of mammalian cells.

[...]

Carl Nathan¹•Institutions (1)

Cornell University¹

01 Sep 1992-The FASEB Journal

TL;DR: How different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule is reviewed.

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Abstract: Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.

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4,149 citations

Journal Article•DOI•

Superoxide Radical and Superoxide Dismutases

[...]

Irwin Fridovich¹•Institutions (1)

Duke University¹

01 Jan 1995-Annual Review of Biochemistry

TL;DR: O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing-inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH..

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Abstract: O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing-inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH.. SODs inhibit such HO. production by scavengingO2-, but Cu, ZnSODs, by virtue of a nonspecific peroxidase activity, may peroxidize spin trapping agents and thus give the appearance of catalyzing OH. production from H2O2. There is a glycosylated, tetrameric Cu, ZnSOD in the extracellular space that binds to acidic glycosamino-glycans. It minimizes the reaction of O2- with NO. E. coli, and other gram negative microorganisms, contain a periplasmic Cu, ZnSOD that may serve to protect against extracellular O2-. Mn(III) complexes of multidentate macrocyclic nitrogenous ligands catalyze the dismutation of O2- and are being explored as potential pharmaceutical agents. SOD-null mutants have been prepared to reveal the biological effects of O2-. SodA, sodB E. coli exhibit dioxygen-dependent auxotrophies and enhanced mutagenesis, reflecting O2(-)-sensitive biosynthetic pathways and DNA damage. Yeast, lacking either Cu, ZnSOD or MnSOD, are oxygen intolerant, and the double mutant was hypermutable and defective in sporulation and exhibited requirements for methionine and lysine. A Cu, ZnSOD-null Drosophila exhibited a shortened lifespan.

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3,298 citations