Superoxide radicals as precursors of mitochondrial hydrogen peroxide

Loschen, G.; Azzi, Angelo; Richter, Christoph; Flohé, Leopold

doi:10.1016/0014-5793(74)80281-4

Cited by 580 publications

(298 citation statements)

References 15 publications

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“…Superoxide can also be generated from several sites in mitochondria (Loschen et al, 1974;Starkov et al, 2004); however, neuronal superoxide production after zinc exposure was unaffected by inhibiting glucose-derived substrate delivery to mitochondria with 500 mmol/L of the glycolysis inhibitor iodoacetate. NADPH oxidase requires glucose for regeneration of NADPH by the hexose monophosphate shunt (Decoursey and Ligeti, 2005).…”

Section: Zinc-induced Reactive Oxygen Species Production Is Mediated mentioning

confidence: 99%

Sequential Release of Nitric Oxide, Zinc, and Superoxide in Hypoglycemic Neuronal Death

Suh

Hamby

Gum

et al. 2008

J Cereb Blood Flow Metab

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Oxidative stress and zinc release are both known to contribute to neuronal death after hypoglycemia; however, the cause-effect relationships between these events are not established. Here we found, using a rat model of profound hypoglycemia, that the neuronal zinc release and translocation that occur immediately after hypoglycemia are prevented by the nitric oxide synthase inhibitor 7-nitroindazole but not by overexpression of superoxide dismutase-1 (SOD-1). However, overexpression of SOD-1 prevented activation of poly(ADP-ribose) polymerase-1 (PARP-1) and neuronal death, suggesting that zinc release is upstream of superoxide production. Accordingly, zinc-induced superoxide production was blocked in neuronal cultures by the NADPH oxidase inhibitor apocynin and by genetic deficiency in the p47 phox subunit of NADPH oxidase. A key role for the vesicular zinc pool in this process was suggested by reduced superoxide formation and neuronal death in mice deficient in zinc transporter 3. Together, these findings suggest a series of events in which nitric oxide production triggers vesicular zinc release, which in turn activates NADPH oxidase and PARP-1. This sequence may also occur in other central nervous system disorders in which zinc, nitric oxide, and oxidative stress have been linked.

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Section: Zinc-induced Reactive Oxygen Species Production Is Mediated mentioning

confidence: 99%

Sequential Release of Nitric Oxide, Zinc, and Superoxide in Hypoglycemic Neuronal Death

Suh

Hamby

Gum

et al. 2008

J Cereb Blood Flow Metab

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“…Superoxide and H 2 O 2 are generated by a variety of oxidoreductases (6) by a leak of electrons to O 2 from the mitochondrial electron transport chain at Complex III (7,8), redox cycling of quinones (9) and numerous other autooxidation reactions. Although cells can respond to generation of H 2 O 2 regardless of its source, the stimulated production of H 2 O 2 that is associated with physiological signaling is more likely due to the oxidoreductases known as NADPH oxidases (NOXs).…”

mentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

165

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During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

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“…Clearly, H 2 O 2 of mitochondrial origin, since the times of its discovery [3,11], considered to represent a disastrous construction failure of the respiratory chain, has been recognized, i.a., as a regulator of cell death pathways [2,6]. Long ago, the superoxide anion, which first attracted the interest of gas-phase physico-chemists [9], radiologist, and toxicologists, has become known to be a physiological R. Brigelius-Flohé (&) German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany e-mail: flohe@dife.de metabolite of the phagocytes' NOX2 [1] that is of outstanding importance in the defence against microbial infections.…”

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confidence: 99%

Commentary: oxidative stress reconsidered

Brigelius‐Flohé

2009

Genes Nutr

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All definitions of the terms 'oxidative stress' and 'antioxidants' implicate that oxidants are just damaging. However, there is increasing evidence that reactive oxygen species (ROS) are not only toxic but that we need them for healthy life. This change in paradigm has been discussed at the third international symposium on 'Nutrition, oxygen biology and medicine-micronutrients, exercise, energy and aging disorders

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Superoxide radicals as precursors of mitochondrial hydrogen peroxide

Cited by 580 publications

References 15 publications

Sequential Release of Nitric Oxide, Zinc, and Superoxide in Hypoglycemic Neuronal Death

Sequential Release of Nitric Oxide, Zinc, and Superoxide in Hypoglycemic Neuronal Death

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Commentary: oxidative stress reconsidered

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