Proteomic analysis of protein tyrosine nitration after ischemia reperfusion injury: Mitochondria as the major target

Liu, Bin; Tewari, Arun K.; Zhang, Liwen; Green‐Church, Kari B.; Zweíer, Jay L.; Chen, Yeong Renn; He, Guanglong

doi:10.1016/j.bbapap.2008.12.008

Cited by 107 publications

(91 citation statements)

References 54 publications

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“…29,34 The presence of nitrated proteins has been implicated in many disease states including I/R injury. 35,36 Our data showed that the tissue protein levels of nitrotyrosine were much higher after I/R relative to the sham-operated rats. Therefore, we hypothesized that the nitrated proteins may experience a loss of function, which attenuates protective roles and contributes to I/R-associated vascular injury.…”

Section: Discussionmentioning

confidence: 61%

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Zhao

et al. 2013

Laboratory Investigation

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Ischemic preconditioning (IPC) strongly protects against ischemia/reperfusion (I/R) injury; however, the molecular mechanism involved in delayed preconditioning-induced endothelial protection in peripheral arteries is unknown. Therefore, we examined using functional, morphologic and molecular biologic studies whether delayed IPC decreases formation of reactive oxygen species and upregulates endothelial nitric oxide synthase (eNOS) that in turn contributes to vascular endothelial protection. Adult male Sprague-Dawley rats were subjected to 30-min ischemia induced by mesenteric artery occlusion followed by 60-min reperfusion 24 h after sham surgery or preconditioning (three cycles of 5-min ischemia/5-min reperfusion). Delayed preconditioning prevented the I/R-induced impairment of endothelium-dependent relaxations to acetylcholine (maximal relaxation: sham 91.4 ± 2.2%; I/R 54.0 ± 4.0%; IPC 80.2 ± 6.3%). This protective effect was abolished by NOS inhibitor N G -nitro-L-arginine methyl ester and not changed by ascorbic acid. Electron microscopy showed marked endothelial damage after I/R and the ultrastructural changes were prevented by delayed preconditioning. Following I/R, the impairment of eNOS phosphorylation and expression was observed in mesenteric vessels. Furthermore, phosphatidylinositol 3-kinase (PI3K) and Akt phosphorylation were reduced, although total PI3K and Akt remained unchanged. IPC restored I/R-induced impairment of eNOS expression and activity. This was possibly the result of the recovery of PI3K/Akt phosphorylation. Furthermore, I/R increased serum level of malondialdehyde, intravascular superoxide and nitrotyrosine generation, which were abrogated by IPC. These results suggest that delayed preconditioning prevented I/R-induced endothelial injury in peripheral resistance vasculature, both in terms of functional and structural changes. Endothelial protection afforded by delayed IPC is associated with inhibition of oxidative stress and upregulation of PI3K/Akt/eNOS pathway.

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Section: Discussionmentioning

confidence: 61%

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Zhao

et al. 2013

Laboratory Investigation

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“…Impaired cellular oxidative metabolism is observed in patients with mutations on the NDUFS1 gene. 43 The Rieske subunit is also a component of the iron-sulfur fragment of cytochrome bc1 complex and transfers electrons to cytochrome c. Liu et al 44 showed that 4 subunits from the ETC including the Rieske subunit were remarkably nitrated at the tyrosine residues in the ischemicreperfused heart. Thus, deacetylation of these proteins might protect them from detrimental protein modifications during ischemia/reperfusion.…”

Section: Shinmura Et Al Cr Primes Mitochondria For Ischemic Stress 403mentioning

confidence: 99%

Caloric Restriction Primes Mitochondria for Ischemic Stress by Deacetylating Specific Mitochondrial Proteins of the Electron Transport Chain

Shinmura

Tamaki

Sano

et al. 2011

Circulation Research

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Rationale: Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD ؉ -dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of specific mitochondrial proteins during CR preserves mitochondrial function and attenuates production of reactive oxygen species during ischemia/reperfusion. Objective:The objectives of the present study were (1) to investigate the effect of CR on mitochondrial function and mitochondrial proteome and (2) to investigate what molecular mechanisms mediate CR-induced cardioprotection. Methods and Results:Male 26-week-old Fischer344 rats were randomly divided into ad libitum-fed and CR (40% reduction) groups for 6 months. No change was observed in basal mitochondrial function, but CR preserved postischemic mitochondrial respiration and attenuated postischemic mitochondrial H 2 O 2 production. CR decreased the level of acetylated mitochondrial proteins that were associated with enhanced Sirtuin activity in the mitochondrial fraction. We confirmed a significant decrease in the acetylated forms of NDUFS1 and cytochrome bc1 complex Rieske subunit in the CR heart. Low-dose Resveratrol treatment mimicked the effect of CR on deacetylating them and attenuated reactive oxygen species production during anoxia/reoxygenation in cultured cardiomyocytes without changing the expression levels of manganese superoxide dismutase. Treatment with nicotinamide completely abrogated the effect of low-dose Resveratrol. Key Words: ischemia Ⅲ mitochondria Ⅲ nutrition Ⅲ reactive oxygen species Ⅲ reperfusion T he prevalence of cardiovascular diseases increases with age. 1 Mortality of coronary artery disease in the elderly is higher than that in the middle-aged. 2,3 Consistent with clinical investigations, experimental studies demonstrate that hearts from senescent animals are more susceptible to ischemia than those from young animals. 4 -6 Both age-related increased prevalence of systemic diseases, referred to as cardiovascular risk factors, and development of cardiovascular aging contribute to the association between aging and cardiovascular diseases. 1 Therefore, development of novel therapeutics for the purpose of controlling cardiovascular aging is urgently required to provide for population aging in developed countries. Conclusions:Caloric restriction (CR) has been widely investigated in experimental animals as a powerful intervention that can prevent and reverse age-related changes. [7][8][9] The daily caloric intake in CR-treated animals was 50% to 70% of the average food intake of animals fed ad libitum (AL). Although there is no evidence stating that CR prolongs lifespan in humans, it markedly increases life span in several species, including rhesus monkey. 7,10 In addition, there is mounting evidence Original received February 17, 2011; revision received June 14, 2011; accepted J...

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“…ROS production increases during ischemia until the O 2 is exhausted; then, it may further increase in early reperfusion (17,89,191,220,396,401). In ischemic hearts, the pH falls to 6.8 or less, but abruptly rises with reperfusion.…”

Section: Executive Summary and Conclusionmentioning

confidence: 99%

“…This inhibition can be transformed into irreversible alterations of respiratory chain when NO reacting with O 2 -generates a great amount of ONOO -, an RNS that can produce irreversible nitration of proteins, including proteins from the oxidative phosphorylation system (18,220,362,391). Under certain conditions, such as scarcity of substrate and/or cofactors, NOS can become uncoupled, resulting in the generation of O 2 -and/or OH , instead of NO (18,379).…”

Section: Ros and Rns Such As Omentioning

confidence: 99%

Mitochondrial Pathways, Permeability Transition Pore, and Redox Signaling in Cardioprotection: Therapeutic Implications

Penna

Perrelli²,

Pagliaro³

2013

Antioxidants & Redox Signaling

152

133

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Reperfusion therapy is the indispensable treatment of acute myocardial infarction (AMI) and must be applied as soon as possible to attenuate the ischemic insult. However, reperfusion is responsible for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore (mPTP). A great part of reperfusion injury occurs during the first minute of reperfusion. The prolonged opening of mPTP is considered one of the endpoints of the cascade to myocardial damage, causing loss of cardiomyocyte function and viability. Opening of mPTP and the consequent oxidative stress due to reactive oxygen and nitrogen species (ROS/RNS) are considered among the major mechanisms of mitochondrial and myocardial dysfunction. Kinases and mitochondrial components constitute an intricate network of signaling molecules and mitochondrial proteins, which interact in response to stressors. Cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning (PostC), obtained with brief intermittent ischemia or with pharmacological agents, which drastically reduce the lethal ischemia/reperfusion injury. The protective pathways converging on mitochondria may preserve their function. Protection involves kinases, adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP modulation. Some clinical studies using ischemic PostC during angioplasty support its protective effects, and an interesting alternative is pharmacological PostC. In fact, the mPTP desensitizer, cyclosporine A, has been shown to induce appreciable protections in AMI patients. Several factors and comorbidities that might interfere with cardioprotective signaling are considered. Hence, treatments adapted to the characteristics of the patient (i.e., phenotype oriented) might be feasible in the future. Antioxid. Redox Signal. 00, 000-000.

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Proteomic analysis of protein tyrosine nitration after ischemia reperfusion injury: Mitochondria as the major target

Cited by 107 publications

References 54 publications

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Caloric Restriction Primes Mitochondria for Ischemic Stress by Deacetylating Specific Mitochondrial Proteins of the Electron Transport Chain

Mitochondrial Pathways, Permeability Transition Pore, and Redox Signaling in Cardioprotection: Therapeutic Implications

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