Thiol chemistry and specificity in redox signaling

Winterbourn, Christine C.; Hampton, Mark B.

doi:10.1016/j.freeradbiomed.2008.05.004

Cited by 1,100 publications

(922 citation statements)

References 205 publications

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“…Recently, it also became evident that a number of drugs, such as antiinflammatory drugs, statins, and antibiotics, which supposedly aimed at different targets in unlike disorders, have the regulation of oxidative stress as a prominent mode of action, thus potentiating the widespread awareness of the role that oxidative stress plays in several diseases and injuries (3,27,47,55,64,155,175,188,209,228,312,336). Superoxide dismutase is an endogenous and first-line-of-defense enzyme that eliminates superoxide by catalyzing its dismutation into O 2 and H 2 O 2 (119,120,212,240).…”

Section: B Antioxidantsmentioning

confidence: 99%

“…Whatever mechanism is in action, antioxidants would also decrease the levels of oxidatively modified biologic molecules. Reactive species, such as O 2 ·À , H 2 O 2 , and · NO, and oxidatively modified biologic molecules (e.g., nitrated lipids and nitrosated proteins) all appear to be involved in signaling events; their removal affects both primary oxidative damage and redox-based cellular transcriptional activity (27,47,55,188,273,298,312,336). Therefore, antioxidants influence both inflammatory and immune pathways and also modulate secondary oxidativestress processes.…”

Section: B Antioxidantsmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

470

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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Section: B Antioxidantsmentioning

confidence: 99%

Section: B Antioxidantsmentioning

confidence: 99%

mentioning

confidence: 99%

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Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

470

689

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“…A change in a single Cys residue is sufficient to have a profound effect on the molecular architecture of PTPases and thus on their enzymatic activity (Mayadas and Wagner, 1992;Chiarugi et al, 2001;Paget and Buttner, 2003;Tonks, 2005;Zimmermann et al, 2007;Winterbourn and Hampton, 2008;Álvarez et al, 2009;Bucciarelli et al, 2009). With this in mind, we searched the protein homology of ZmRIP1 and found that distinct differences between ZmRIP1 and its homologs exist in the Cys residues at two sites (i.e.…”

Section: Discussionmentioning

confidence: 99%

Purification and Characterization of ZmRIP1, a Novel Reductant-Inhibited Protein Tyrosine Phosphatase from Maize

Zhao²,

Liang³

et al. 2012

Plant Physiology

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Protein tyrosine phosphatases (PTPases) have long been thought to be activated by reductants and deactivated by oxidants, owing to the presence of a crucial sulfhydryl group in their catalytic centers. In this article, we report the purification and characterization of Reductant-Inhibited PTPase1 (ZmRIP1) from maize (Zea mays) coleoptiles, and show that this PTPase has a unique mode of redox regulation and signaling. Surprisingly, ZmRIP1 was found to be deactivated by a reductant. A cysteine (Cys) residue (Cys-181) near the active center was found to regulate this unique mode of redox regulation, as mutation of Cys-181 to arginine-181 allowed ZmRIP1 to be activated by a reductant. In response to oxidant treatment, ZmRIP1 was translocated from the chloroplast to the nucleus. Expression of ZmRIP1 in Arabidopsis (Arabidopsis thaliana) plants and maize protoplasts altered the expression of genes encoding enzymes involved in antioxidant catabolism, such as At1g02950, which encodes a glutathione transferase. Thus, the novel PTPase identified in this study is predicted to function in redox signaling in maize.

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“…Thioredoxin are enzymes that play key roles in cell biology, among them as hydrogen donors for the reduction of ribonucleotides to deoxyribonucleotides (building blocks of DNA) [17]; and as substrates for peroxiredoxin, the most relevant cellular pathway for removal of hydroperoxides [18]. Thioredoxins are thiol-disulfide oxido-reductases of about 12 kDa; they display a Trp-Cys-Gly-Pro-Cys motif that reversibly switches between the disulfide and dithiol states.…”

Section: Introductionmentioning

confidence: 99%