Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases

Aoyama, Koji; Matsubara, Kazuo; Fujikawa, Y.; Nagahiro, Yukio; Shimizu, Keiko; Umegae, Nobuyuki; Hayase, Nobumasa; Shiono, Hiroshi; Kobayashi, Shotai

doi:10.1002/1531-8249(200004)47:4<524::aid-ana19>3.0.co;2-5

Cited by 113 publications

(31 citation statements)

References 18 publications

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“…3). The activation was also observed with cytochrome c treated with a single low dose (50 mM) of perox- 18 Vol. 30, No.…”

Section: Nitration Of Cytochrome C By Continuous Peroxynitrite Infusimentioning

confidence: 72%

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Nitration of Specific Tyrosine Residues of Cytochrome c Is Associated with Caspase-Cascade Inactivation

Nakagawa

Komai

Takusagawa

et al. 2007

Biological & Pharmaceutical Bulletin

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“…3). The activation was also observed with cytochrome c treated with a single low dose (50 mM) of perox- 18 Vol. 30, No.…”

Section: Nitration Of Cytochrome C By Continuous Peroxynitrite Infusimentioning

confidence: 72%

“…other neurodegenerative diseases, 17,18) and sepsis. 19,20) Peroxynitrite causes nitration of free tyrosine and protein tyrosine residues.…”

mentioning

confidence: 99%

Nitration of Specific Tyrosine Residues of Cytochrome c Is Associated with Caspase-Cascade Inactivation

Nakagawa

Komai

Takusagawa

et al. 2007

Biological & Pharmaceutical Bulletin

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“…Nitration of tyrosine residues by peroxynitrite is quite selective for tyrosines in which the aromatic ring is near the surface, there is nearby negative charge, and there are no proximal cysteines [13]. Nitration of Tyr-34 leads to complete inactivation of SOD2 and promotes additional peroxynitrite formation [14], and has been seen in patients with neurodegenerative diseases [40]. Therefore, in some situations peroxynitrite activates a positive feedback loop that increases oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Blockade of neuronal nitric oxide synthase reduces cone cell death in a model of retinitis pigmentosa

Komeima

Usui

Shen

et al. 2008

Free Radical Biology and Medicine

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Retinitis pigmentosa (RP) is a group of diseases in which many different mutations cause rod photoreceptor cells to die and then gradually cone photoreceptors die due to progressive oxidative damage. In this study, we have shown that peroxynitrite-induced nitrosative damage also occurs. In the rd1 mouse model of RP, there was increased staining for S-nitrosocysteine and nitrotyrosine protein adducts that are generated by peroxynitrite. Peroxynitrite is generated from nitric oxide (NO) and superoxide radicals. After degeneration of rods, injection of hydroethidine resulted in strong fluorescence in the retina of rd1 mice indicating high levels of superoxide radicals, and this was reduced, as was nitrotyrosine staining, by apocynin suggesting that over action of NADP(H) oxidase is at least partially responsible. Treatment of rd1 mice with a mixture of nitric oxide synthase (NOS) inhibitors markedly reduced S-nitrosocysteine and nitrotyrosine staining and significantly increased cone survival, indicating that NO-derived peroxynitrite contributes to cone cell death. Treatment with 7-nitroindazole, a relatively specific inhibitor of neuronal NOS, also significantly reduced cone cell death, but aminoguanidine, a relatively specific inhibitor of inducible NOS, did not. These data suggest that NO generated by neuronal NOS exacerbates oxidative damage to cones in RP and that combined therapy to reduce NO and oxidative stress should be considered.

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“…Tyrosine nitration is involved in many postischemic modifications [55][56][57]. Examples of proteins susceptible to inactivation by tyrosine nitration include mitochondrial superoxide dismutase [58,59] and several enzymes involved in oxidative energy metabolism, including aconitase [60], glutamate dehydrogenase [46], α-ketoglutarate dehydrogenase [61], and PDHC [46]. Because PDHC and α-ketoglutarate dehydrogenase complex share similar reaction mechanisms and an identical polypeptide subunit (E3), it is not surprising that they are both sensitive to enzyme inhibition by tyrosine nitration.…”

Section: Discussionmentioning

confidence: 99%

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

Richards

Rosenthal

Kristián

et al. 2006

Free Radical Biology and Medicine

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The pyruvate dehydrogenase complex (PDHC) is a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate and represents the sole bridge between anaerobic and aerobic cerebral energy metabolism. Previous studies demonstrating loss of PDHC enzyme activity and immunoreactivity during reperfusion after cerebral ischemia suggest that oxidative modifications are involved. This study tested the hypothesis that hyperoxic reperfusion exacerbates loss of PDHC enzyme activity, possibly due to tyrosine nitration or S-nitrosation. We used a clinically relevant canine ventricular fibrillation cardiac arrest model in which, after resuscitation and ventilation on either 100% O 2 (hyperoxic) or 21-30% O 2 (normoxic), animals were sacrificed at 2 h reperfusion and the brains removed for enzyme activity and immunoreactivity measurements. Animals resuscitated under hyperoxic conditions exhibited decreased PDHC activity and elevated 3-nitrotyrosine immunoreactivity in the hippocampus but not the cortex, compared to nonischemic controls. These measures were unchanged in normoxic animals. In vitro exposure of purified PDHC to peroxynitrite resulted in a dose-dependent loss of activity and increased nitrotyrosine immunoreactivity. These results support the hypothesis that oxidative stress contributes to loss of hippocampal PDHC activity during cerebral ischemia and reperfusion and suggest that PDHC is a target of peroxynitrite. KeywordsMitochondria; Hyperoxia; Nitrotyrosine; Normoxia; Oxidative stress; Global ischemia; Selective vulnerability; Free radicals Global cerebral ischemia and reperfusion cause severe neurochemical alterations, including oxidative modifications to lipids, proteins, and DNA. These and other covalent modifications can impair enzyme activities, including those necessary for energy metabolism. Alterations in these enzyme activities can limit postischemic aerobic metabolism and cellular ATP regeneration, thereby contributing to the pathophysiology of delayed neuronal cell death [1][2][3][4]. One enzyme known to be targeted and inactivated by reactive oxygen species is the pyruvate dehydrogenase complex (PDHC) [5]. Effects of ischemia/reperfusion on the PDHC can be particularly devastating because this enzyme forms the bridge between glycolysis and the Krebs cycle and can be the rate-limiting step in aerobic cerebral energy metabolism. NIH Public Access Author ManuscriptFree Radic Biol Med. Author manuscript; available in PMC 2008 October 21. Published in final edited form as:Free Radic Biol Med. 2006 June 1; 40(11): 1960-1970. doi:10.1016/j.freeradbiomed.2006.01.022. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe PDHC is located exclusively in the mitochondrial matrix and catalyzes the oxidative decarboxylation of pyruvate to form NADH and acetyl coenzyme A-the primary form of carbon that enters the Krebs cycle in the adult brain. Several laboratories have shown that PDHC enzyme activity is lost during cerebral ischemia/reperfusion [6][7][8]. PDHC im...

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Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases

Cited by 113 publications

References 18 publications

Nitration of Specific Tyrosine Residues of Cytochrome c Is Associated with Caspase-Cascade Inactivation

Nitration of Specific Tyrosine Residues of Cytochrome c Is Associated with Caspase-Cascade Inactivation

Blockade of neuronal nitric oxide synthase reduces cone cell death in a model of retinitis pigmentosa

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

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