A new look at a time-worn system: oxidation of CuZn-SOD by H2O2

Jewett, Sandra L.; Rocklin, Amy M.; Ghanevati, Mahin; Abel, Jeffrey M.; Marach, Jaime A.

doi:10.1016/s0891-5849(98)00274-3

Cited by 67 publications

(44 citation statements)

References 49 publications

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“…Unfortunately, native SOD cannot be used effectively due to recognized problems with its short half-life, poor bioavailability, and immunogenicity [13], [14] and [15]. Furthermore, SOD can have pro-oxidant activities at higher concentrations, e.g., Cu/ZnSOD can promote the generation of hydroxyl radicals [16] and [48] and inhibit the ability of superoxide to regulate lipid peroxidation [19] and [49]. This has generated much interest in SODm, leading to the development of agents including macrocyclics, manganese salens, nitroxides, porphyrins, and many other catalytic antioxidants [15], [20], [50], [51], [52], [53], [54] and [55].…”

Section: Discussionmentioning

confidence: 99%

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Samai

Hague

Naughton

et al. 2008

Free Radical Biology and Medicine

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Section: Discussionmentioning

confidence: 99%

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Samai

Hague

Naughton

et al. 2008

Free Radical Biology and Medicine

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“…Immunoprecipitations of rat Cu/Zn SOD and probing for nitrotyrosine residues revealed that Cu/Zn SOD is not nitrated (data not shown). It is possible that some Cu/Zn SOD is inactivated via peroxidation and/or oxidation of the active site histidine (25). It is logical to speculate that the rise in peroxide levels after reperfusion could modify Cu/Zn SOD in this manner.…”

Section: Discussionmentioning

confidence: 99%

Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression

Montalto

Hart

Jordan

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression. Am J Physiol Gastrointest Liver Physiol 285: G197-G206, 2003. First published March 13, 2003 10.1152/ajpgi.00029.2003.-Inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) play an important role in the pathology of ischemia-reperfusion. This study sought to determine if the proinflammatory effects of complement modulate iNOS and SOD in the rat after gastrointestinal ischemia and reperfusion (GI/R). An inhibitory or noninhibitory anti-complement component 5 (C5) monoclonal antibody (18A or 16C, respectively) was administered before GI/R. RT-PCR revealed a significant increase in intestinal iNOS mRNA compared with sham after GI/R that was attenuated significantly by 18A. Immunohistochemistry demonstrated increased iNOS protein expression within the intestinal crypts after GI/R. Cu/Zn SOD (mRNA and protein) was unaffected by GI/R, whereas Cu/Zn SOD activity was reduced significantly. Mn SOD protein expression was decreased significantly by GI/R. Anti-C5 preserved Cu/Zn SOD activity and Mn SOD protein expression. Staining for nitrotyrosine showed that anti-C5 treatment reduced protein nitration in the reperfused intestine. Immunohistochemistry demonstrated prominent phosphorylated (p) inhibitory factor-B (I B)-␣ staining of intestinal tissue after GI/R, whereas anti-C5 reduced p-I B-␣ expression. These data indicate that complement may mediate tissue damage during GI/R by increasing intestinal iNOS and decreasing the activity and protein levels of Cu/Zn SOD and Mn SOD, respectively. ischemia-reperfusion; inhibitory factor-B; interleukin-1␤ GASTROINTESTINAL ISCHEMIA-reperfusion (GI/R) is a common clinical problem in the settings of sepsis, hemorrhagic shock, vascular surgery, and small bowel transplantation (17, 21). GI/R causes gut dysfunction characterized by histological evidence of impaired gut motility, increased intestinal permeability, and mucosal injury (18). Numerous mediators have been implicated in GI/R injury, including cytokines (8,15,43,54,55) NF-B is maintained in a latent form in the cytoplasm of cells where it is complexed to inhibitory factor-B (I B) proteins (24). Upon activation of NF-B, I B is phosphorylated (p) by I B kinases at two conserved serine residues in the NH 2 terminus, which targets the protein for ubiquination and degradation by the proteosome. This rapidly frees NF-B to translocate to the nucleus, where it upregulates the transcription of a variety of adhesion molecules (ICAM-1 and VCAM-1), cytokines (TNF, IL-1, and IL-6), and enzymes (iNOS; see Refs. 24 and 37).NO has been implicated as a mediator of tissue damage in several models of intestinal disease, including reperfusion injury (26,47,48). NO can be produced by three nitric oxide synthase (NOS) isoforms (neuronal NOS, iNOS, and endothelial NOS). Specific inhibition of iNOS has been shown to attenuate NO production significantly and decrease intestinal injury, indicating that iNOS mediates the excessive p...

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“…7 Thus, these findings suggest that the conformation of the active copper-binding site of SOD3 may resemble the active site of SOD1. The rate constants for dismutation of O 2 ⅐Ϫ by SOD1 and SOD3 are similar, and both enzymes are inhibited by cyanide, azide, and diethyldithiocarbamate. 9 Because SOD3 constitutes 30% to 50% of the total SOD in vascular tissues 10 and is localized in the extracellular space, it would be of considerable importance to determine whether SOD3 also has peroxidase activity and to determine which small molecule reductants can preserve its dismutase activity.…”

Section: See Page 1367mentioning

confidence: 95%

Peroxidase Properties of Extracellular Superoxide Dismutase

Hink

Santanam

Dikalov

et al. 2002

ATVB

187

133

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Objective-The cytosolic form of Cu/Zn-containing superoxide dismutase (SOD1) has peroxidase activity, with H 2 O 2 used as a substrate to oxidize other molecules. We examined peroxidase properties of the extracellular form of SOD (SOD3), a major isoform of SOD in the vessel wall, by using recombinant SOD3 and an in vivo model of atherosclerosis. Methods and Results-In the presence of HCO 3 Ϫ , SOD3 reacted with H 2 O 2 to produce a hydroxyl radical adduct of the spin trap 5-diethoxyphosphoryl-5methyl-1-pyrroline N-oxide (DEMPO). SOD1 and SOD3 were inactivated by H 2 O 2 in a dose-and time-dependent fashion, and this was prevented by physiological levels of uric acid. To examine the in vivo role of uric acid on SOD1 and SOD3, control and apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) mice were treated with oxonic acid, which inhibits urate metabolism. This treatment increased plasma levels of uric acid in control and ApoE Ϫ/Ϫ mice by Ϸ3-fold. Although increasing uric acid levels did not alter aortic SOD1 and SOD3 protein expression, aortic SOD1 and SOD3 activities were increased by 2-to 3-fold in aortas from ApoE Ϫ/Ϫ mice but not in aortas from control mice. Conclusions-These studies show that SOD1 and SOD3 are partially inactivated in atherosclerotic vessels of ApoE See page 1367Extracellular SOD (SOD3) is also a Cu/Zu-containing SOD that shares Ϸ50% sequence homology with SOD1 within its catalytic region. 7 Compared with the x-ray crystallography structure data for SOD1, 8 all ligands to the copper and zinc atoms can be identified in SOD3, as can the cysteines forming the intramolecular disulfide bond. 7 Thus, these findings suggest that the conformation of the active copper-binding site of SOD3 may resemble the active site of SOD1. The rate constants for dismutation of O 2 ⅐Ϫ by SOD1 and SOD3 are similar, and both enzymes are inhibited by cyanide, azide, and diethyldithiocarbamate. 9 Because SOD3 constitutes 30% to 50% of the total SOD in vascular tissues 10 and is localized in the extracellular space, it would be of considerable importance to determine whether SOD3 also has peroxidase activity and to determine which small molecule reductants can preserve its dismutase activity.Although peroxidase properties of SOD1 have been studied extensively in vitro, evidence is lacking to prove that either SOD1 or SOD3 activities are affected by H 2 O 2 in vivo. In the present study, we sought to determine whether SOD3 has peroxidase activities that are similar to those of SOD1 and to examine small molecules that might prevent the inactivation of SOD3 by using recombinant SOD3 expressed in Pichia pastoris. In these experiments, we found that physiological levels of uric acid completely prevented the inactivation of SOD1 and SOD3 by H 2 O 2 . In additional experiments, we provide evidence for peroxidase activity of SOD1 and SOD3 in vivo, by showing that these enzymes seem to be partially inactivated in the aortas of apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) mice and that the activity of these

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A new look at a time-worn system: oxidation of CuZn-SOD by H2O2

Cited by 67 publications

References 49 publications

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression

Peroxidase Properties of Extracellular Superoxide Dismutase

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