Mechanisms of Oxidation with Oxygen

Taube, Henry

doi:10.1085/jgp.49.1.29

Cited by 139 publications

(71 citation statements)

References 23 publications

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“…The electronic structure of dioxygen, in its ground state, and the dictates of quantum mechanics, lead to a spin restriction which actually favors the univalent pathway of oxygen redution (1)(2)(3)(4)(5). This most facile route of dioxygen reduction generates, in turn, the superoxide radical (02), hydrogen peroxide (H2~)' the hydroxyl radical (.…”

Section: Some Biological Sources Of Superoxidementioning

confidence: 99%

Superoxide Radical and Superoxide Dismutases

Fridovich¹

1981

Topics in Environmental Physiology and Medicine

331

337

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The metalloenzymes that have been named superoxide dismutases have several attributes. They are abundant, widely distributed, essential as a defense against oxygen toxicity; they are also unique among enzymes in that their natural substrate is an unstable free radical. They are evolution's answer to the biological production of the superoxide radical (0 2 ), This free radical, previously considered only in connection with the high energy irradiation of oxygenated aqueous media, is also produced under ordinary circumstances within respiring cells. The superoxide radical is intrinsically reactive and can furthermore engender other enormously reactive radicals and excited states which are potentially capable of destroying the delicate chemical architecture of the cell. The intermediates of oxygen reduction, i.e., O 2 , H 2 0 2 , and OH', are the primary cause of oxygen toxicity; the enzymes, which catalytically scavenge them or prevent their production, are the foremost defenses which limit that toxicity. H2~ and the catalases anc! peroxidases, which scavenge it, are discussed in other chapters of this volume. We shall devote ourselves to superoxide and the superoxide dismutases.

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Section: Some Biological Sources Of Superoxidementioning

confidence: 99%

Superoxide Radical and Superoxide Dismutases

Fridovich¹

1981

Topics in Environmental Physiology and Medicine

331

337

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“…are the intermediates formed during the progressive univalent reduction ofdioxygen (1)(2)(3). These intermediates are very reactive and are normally generated in respiring cells (3) as well as during exposure to ionizing radiation (4,5).…”

mentioning

confidence: 99%

Mutagenicity of oxygen free radicals.

Moody¹,

Hassan²

1982

Proc. Natl. Acad. Sci. U.S.A.

209

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Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride) was used as an intracellular generator of oxygen free radicals and was found to be highly mutagenic for Salmonella typhmunnum. It caused both base-pair substitution and frameshift mutations. Paraquat was much more toxic and mutagenic in a simple nutritionally restricted medium than in a rich complex medium. The mutagenicityofparaquatwas dependent upon the presence ofa supply ofboth electrons and oxygen. Cells containing high levels of superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1. 15. 1.1) were more resistant to the toxicity and the mutagenicity ofparaquat than were cells containing normal levels of this enzyme. The mutagenicity of paraquat thus appears to be due to its ability to exacerbate the intracellular production of superoxide radicals.Superoxide anion radicals (2-), hydrogen peroxide (H202), and hydroxyl radicals (OH.) are the intermediates formed during the progressive univalent reduction ofdioxygen (1-3). These intermediates are very reactive and are normally generated in respiring cells (3) as well as during exposure to ionizing radiation (4, 5). There is also mounting evidence that the cytotoxicity of certain antitumor compounds and xenobiotic compounds is due to reduced oxygen species produced during redox cycling (6)(7)(8)(9)(10). Oxygen cytotoxicity is held in check by the delicate balance between the rates ofgeneration ofreduced oxygen species and the rate of their removal by the different defensive mechanisms (11); any shift in this delicate balance can lead to cellular damage. Living cells have evolved different defense mechanisms to protect against the deleterious effects of the reduced oxygen species (3,11,12). Superoxide dismutases protect against 02, and hydroperoxidases protect against H202 (11,12).Hyperbaric dioxygen is known to be mutagenic to Escherichia coli (13,14), and physiological concentrations ofdioxygen are mutagenic to certain anaerobic mutants of Salmonella typhimurium (15). It has also been shown that superoxide radicals, generated by xanthine oxidase or by potassium superoxide, cause DNA strand scissions in vitro, and that scavengers of 02, H202, or OH-provide protection (16-18). Paraquat (pQ2+) can act as an in vivo generator of superoxide radical (6,7,(19)(20)(21). It forms a relatively stable, yet oxygen-sensitive, paraquat radical (PQ-+) that reacts very rapidly (k2 = 7.7 x 108 M -' s`) with dioxygen to generate superoxide radical (20). pQ2+, under appropriate conditions, is capable of inducing superoxide dismutase in E. coli (22). This investigation was undertaken to determine if oxygen free radicals, generated by pQ2+, are mutagenic in vivo; the S. typhimurium Ames tester strains TA98 and TA100 were used to test for mutagenicity.MATERIALS AND METHODS Chemicals. pQ2+ (1, 1'-dimethyl-4,4'-bipyridinium dichloride, methyl viologen), mitomycin C, sodium azide, and proflavine were purchased from Sigmat and were dissolved in sterile water just prior to use.Bacterial Strains. S. typhimurium histi...

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“…The chemistry of oxygen dictates that the one-electron reduction that produces O :¡ 2 be predominant (22). Thus, O :¡ 2 is the primary product of biological reduction of oxygen, whereas the major source of H 2 O 2 in cells results from the dismutation of O :¡ 2 .…”

Section: Signaling By Rosmentioning

confidence: 99%

Signaling by the Respiratory Burst in Macrophages

Forman

Torrès²

2001

IUBMB Life

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SummaryDuring phagocytosis or stimulation with a wide variety of agents, macrophages and other phagocytic cells produce reactive oxygen species (ROS) through activation of a multicomponent NADPH oxidase. ROS production through related NADPH oxidases has recently been demonstrated in several other cell types. Furthermore, the physiological generation of ROS production has now been clearly implicated in activating signaling pathways resulting in a broad array of physiological responses from cell proliferation to gene expression and apoptosis. This brief review suggests that: 1) hydrogen peroxide and superoxide, but not the hydroxyl radical, function as second messengers; 2) antioxidant enzymes function in the "turn-off" phase of signal transduction; 3) the chemistry of thiols is critical in redox signaling; and 4) the primary physiological role of the respiratory burst in macrophages may be in redox signaling rather than microbicidal activity. IUBMB INTRODUCTIONOxygen is essential to life and reactive oxygen species (ROS), which include superoxide anion (O :¡ 2 ), hydroxyl radical ( : OH), hydrogen peroxide (H 2 O 2 ), and lipid peroxides (ROOH), which are produced in cells under aerobic conditions. Studies done around 20 years ago had hinted at a role for ROS as second messengers when it was revealed that exogenous H 2 O 2 could mimic the action of the insulin growth factor (1) and that insulin and nerve growth factor stimulated endogenous H 2 O 2 production (2). At that time, the role of ROS in pathology took center stage and researchers focused their attention on the role of phosphorylation of small molecules and proteins as the principal means of transmitting signaling events, pushing signaling by ROS into the background. The more recent discoveries of the activation of several transcription factors by ROS, the role of nitric oxide, a free radical, as a signaling molecule that activates cyclic GMP production (3), and the discovery in many tissues of speci c enzymes as a source of ROS (4-8) stimulated a renaissance in redox signaling studies (see [9][10][11][12][13][14][15] for reviews). Here, we focus on signaling by ROS in macrophages, cells that produce ROS and are exposed to ROS during in ammation.

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Mechanisms of Oxidation with Oxygen

Cited by 139 publications

References 23 publications

Superoxide Radical and Superoxide Dismutases

Superoxide Radical and Superoxide Dismutases

Mutagenicity of oxygen free radicals.

Signaling by the Respiratory Burst in Macrophages

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