Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation

Salvemini, Daniela; Doyle, Tim; Cuzzocrea, Salvatore

doi:10.1042/bst0340965

Cited by 148 publications

(120 citation statements)

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“…Oxidative stress is no exception (39). Reactive oxygen species (ROS) are known to cause persistent pain (40)(41)(42)(43)(44) C111 C164 C239 C264 C269 C369 C393 C397 C540 C586 C624 C641 C722 C748 C772 C783 are indiscriminative (45), compromising multiple cell types to exacerbate tissue inflammation and nociception.…”

Section: Discussionmentioning

confidence: 99%

Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification

Chuang

Lin

2009

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

169

119

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The capsaicin receptor TRPV1, one of the major transduction channels in the pain pathway, integrates information from extracellular milieu to control excitability of primary nociceptive neurons. Sensitization of TRPV1 heightens pain sensation to moderately noxious or even innocuous stimuli. We report here that oxidative stress markedly sensitizes TRPV1 in multiple species' orthologs. The sensitization can be recapitulated in excised insideout membrane patches, reversed by strong reducing agents, and blocked by pretreatment with maleimide that alkylates cysteines. We identify multiple cysteines required for full modulation of TRPV1 by oxidative challenges. Robust oxidative modulation recovers the agonist sensitivity of receptors desensitized by prolonged exposure to capsaicin. Moreover, oxidative modulation operates synergistically with kinase or proton modulations. Thus, oxidative modulation is a robust mechanism tuning TRPV1 activity via covalent modification of evolutionarily conserved cysteines and may play a role in pain sensing processes during inflammation, infection, or tissue injury.covalent modification ͉ pain

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Section: Discussionmentioning

confidence: 99%

Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification

Chuang

Lin

2009

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

169

119

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“…Reactive species, such as nitric oxide ( · NO), superoxide (O 2 ·À ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO -), and others have been widely recognized as signaling species that, by affecting redox-based cellular transcriptional activity, control inflammatory and immune responses and enhance secondary oxidative stress (27,47,96,151,188,273,276,298,335,336). Mitochondria, the major producers of reactive species, are consistently found to play a critical role in oxidative stress (55,155,228,312).…”

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confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

471

689

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Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO 3 _ À , peroxyl radical, and less efficiently H 2 O 2 . By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and=or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877-918.

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“…Increased production of NO by iNOS and reactive oxidants derived from nitric oxide has been proposed to mediate tissue injury in several inflammatory and infectious diseases including hepatic diseases [7,18,19]. NO is able to trigger its own biosynthesis through iNOS induction in macrophages but not in hepatocytes, generating a potent amplification mechanism that may constitute the basis for the excessive formation of NO in acute and chronic inflammatory conditions [4,29].…”

Section: Discussionmentioning

confidence: 99%

“…In biological systems, reaction of NO with superoxide forms peroxynitrite, which is more reactive and damaging than its precursor and has been demonstrated to diffuse freely across phospholipid membrane bilayers and to react with a wide variety of molecular targets, including lipids, DNA and proteins [7]. Peroxynitrite has been implicated in a number of pathological situations, and tyrosine nitration induced by this agent has been reported to increase in various human diseases such as acute and chronic inflammatory processes [8].…”

Section: Introductionmentioning

confidence: 99%

Apoptosis of hepatic stellate cells mediated by specific protein nitration

Mòdol

Natal

Obanos

et al. 2011

Biochemical Pharmacology

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Inflammatory conditions are characterized by continuous overproduction of nitric oxide (NO) that can contribute to cell survival but also to cell demise by affecting apoptosis.These facts are important in regulation of hepatic fibrogenesis during exposure to inflammatory stress, since elevated NO may pose the risk of cells with a pro-fibrogenic phenotype giving rise to a sustained proliferation leading to chronic fibrosis. Since nitration of tyrosine residues occurs in a range of diseases involving inflammation, we tested the hypothesis that nitration of specific proteins could result in apoptosis of hepatic stellate cells (HSC), the primary cellular source of matrix components in liver diseases. We found the peroxynitrite generator SIN-1 to promote apoptosis in human and rat HSC, based on oligonucleosomal DNA fragmentation, caspase-3 and -9 activation, Bcl-2 depletion and accumulation of Bax protein. We also showed that SIN-1-induced apoptosis of HSC was due to protein nitration. Among the tyrosine-nitrated proteins, tyrosine kinase Lyn was identified.SIN-1 triggered a signaling pathway through Src kinase Lyn activation that resulted in increased activity of the tyrosine kinase Syk. The involvement of these signaling molecules in the apoptotic process induced by SIN-1 as well as the mechanism by which they are activated was confirmed by using specific inhibitors. In summary, NO, via protein-nitration, could play an important role in controlling liver fibrosis resolution by regulation of HSC apoptosis.Key Words: peroxynitrite; programmed cell death; inflammation; signaling molecules; fibrosis Page 3 of 37 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 Abbreviations: NO, nitric oxide; iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase; cNOS, constitutive nitric oxide synthase; SIN-1, 3-morpholinosydononimide-HCl; Bax, proapoptotic member of the Bcl-2 family of proteins; NF-B, nuclear factor kappa B; FeTMPyP,[Iron (III) tetrakis(N-methyl-4'-pyrimidyl)porphyrin-5Cl

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Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation

Cited by 148 publications

References 100 publications

Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification

Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Apoptosis of hepatic stellate cells mediated by specific protein nitration

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