Endothelium-Derived Nitric Oxide Regulates Postischemic Myocardial Oxygenation and Oxygen Consumption by Modulation of Mitochondrial Electron Transport

Zhao, Xue; He, Guanglong; Chen, Yeong Renn; Pandian, Ramasamy P.; Kuppusamy, Periannan; Zweíer, Jay L.

doi:10.1161/circulationaha.104.527226

Cited by 114 publications

(153 citation statements)

References 52 publications

Supporting

Mentioning

137

Contrasting

Order By: Relevance

“…The procedure for the in vivo ischemia-reperfusion rat model was performed by the technique reported in the literature (10,25). Sprague-Dawley rats (ϳ300 -350 g) were anesthetized with Nembutal administered intraperitoneally (80 -100 mg/kg).…”

Section: In Vivo Myocardial Regional Ischemia-reperfusion Modelmentioning

confidence: 99%

“…Increased NO production and subsequent peroxynitrite (OONO Ϫ ) formation have been detected in the postischemic heart (10,11,14,15). Alterations in the generation of NO occurring in hearts subjected to ischemia/reperfusion have been linked to NO synthase (NOS)-dependent (10,11,14,15) and NOS-independent (18,19) pathways, including involvement of endothelial NOS (eNOS), increased nitrite disproportionation, and increased expression of inducible NO synthase (iNOS) in chronic reperfusion injury (11). Therefore, myocardial ischemia/reperfusion indirectly changes the balance between NO and ROS (especially O 2 . )…”

mentioning

confidence: 99%

See 1 more Smart Citation

Protein Tyrosine Nitration of the Flavin Subunit Is Associated with Oxidative Modification of Mitochondrial Complex II in the Post-ischemic Myocardium

Chen

Rawale

et al. 2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Increased O 2. and NO production is a key mechanism of mito- To test for protein nitration, rats were subjected to 30 min of coronary ligation followed by 24 h of reperfusion. Tissue homogenates were immunoprecipitated with AbGSC90 and probed with antibodies against 3-nitrotyrosine. Enhancement of protein tyrosine nitration was detected in the post-ischemic myocardium. Isolated SQR was subjected to in vitro protein nitration with peroxynitrite, leading to site-specific nitration at the 70-kDa polypeptide and impairment of SQR electron transfer activity. Protein nitration of SQR further impaired its protein-protein interaction with Complex III. Liquid chromatography/tandem mass spectrometry analysis indicated that Tyr-56 and Tyr-142 were involved in protein tyrosine nitration. When the isolated SQR was subjected to in vitro S-glutathionylation, oxidative modification and impairment mediated by peroxynitrite were significantly decreased, thus confirming the protective effect of S-glutathionylation from the oxidative damage of nitration.

show abstract

Section: In Vivo Myocardial Regional Ischemia-reperfusion Modelmentioning

confidence: 99%

mentioning

confidence: 99%

Protein Tyrosine Nitration of the Flavin Subunit Is Associated with Oxidative Modification of Mitochondrial Complex II in the Post-ischemic Myocardium

Chen

Rawale

et al. 2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The regulation of cellular respiration by NO, through the interaction at CcO in the mitochondrial ETC, has been found to be an important factor in many pathophysiological conditions such as ischemia, hyperthermia, etc. (Basu et al 2008;Ilangovan et al 2004a;Zhao et al 2005). A number of studies have been carried out to unravel the mechanistic details of how NO affects the CcO activity at normal and pathologic conditions (Cleeter et al 1994;Cooper and Davies 2000).…”

Section: Discussionmentioning

confidence: 99%

“…This finding is especially important in terms of the regulation of oxygen consumption in various pathological conditions. For example, an ischemia/reperfusion model of the heart has demonstrated that sudden bursts of NO can be measured, and then the heart returns to its normal state (Zhao et al 2005). The oxygen consumption was proven to be lower in that condition, but it is unclear what mechanism causes such a reduction, especially at a low prevailing pO 2 during ischemia (Zhao et al 2005).…”

Section: Hsp90mentioning

confidence: 99%

“…For example, an ischemia/reperfusion model of the heart has demonstrated that sudden bursts of NO can be measured, and then the heart returns to its normal state (Zhao et al 2005). The oxygen consumption was proven to be lower in that condition, but it is unclear what mechanism causes such a reduction, especially at a low prevailing pO 2 during ischemia (Zhao et al 2005). The present results imply that the decrease in oxygen consumption could be attributed to irreversible binding at Cu B , instead of competitive binding at the heme a 3 site.…”

Section: Hsp90mentioning

confidence: 99%

See 1 more Smart Citation

Activation of Hsp90/NOS and increased NO generation does not impair mitochondrial respiratory chain by competitive binding at cytochrome C Oxidase in low oxygen concentrations

Presley

Vedam

et al. 2009

Cell Stress and Chaperones

Self Cite

View full text Add to dashboard Cite

Nitric oxide (NO) is known to regulate mitochondrial respiration, especially during metabolic stress and disease, by nitrosation of the mitochondrial electron transport chain (ETC) complexes (irreversible) and by a competitive binding at O 2 binding site of cytochrome c oxidase (CcO) in complex IV (reversible). In this study, by using bovine aortic endothelial cells, we demonstrate that the inhibitory effect of endogenously generated NO by nitric oxide synthase (NOS) activation, by either NOS stimulators or association with heat shock protein 90 (Hsp90), is significant only at high prevailing pO 2 through nitrosation of mitochondrial ETC complexes, but it does not inhibit the respiration by competitive binding at CcO at very low pO 2 . ETC complexes activity measurements confirmed that significant reduction in complex IV activity was noticed at higher pO 2 , but it was unaffected at low pO 2 in these cells. This was further extended to heat-shocked cells, where NOS was activated by the induction/activation of (Hsp90) through heat shock at an elevated temperature of 42°C. From these results, we conclude that the entire attenuation of respiration by endogenous NO is due to irreversible inhibition by nitrosation of ETC complexes but not through reversible inhibition by competing with O 2 binding at CcO at complex IV.

show abstract

An Injectable Dual‐Function Hydrogel Protects Against Myocardial Ischemia/Reperfusion Injury by Modulating ROS/NO Disequilibrium

et al. 2022

View full text Add to dashboard Cite

Acute myocardial infarction (MI) is the leading cause of death worldwide. Exogenous delivery of nitric oxide (NO) to the infarcted myocardium has proven to be an effective strategy for treating MI due to the multiple physiological functions of NO. However, reperfusion of blood flow to the ischemic tissues is accompanied by the overproduction of toxic reactive oxygen species (ROS), which can further exacerbate tissue damage and compromise the therapeutic efficacy. Here, an injectable hydrogel is synthesized from the chitosan modified by boronate-protected diazeniumdiolate (CS-B-NO) that can release NO in response to ROS stimulation and thereby modulate ROS/NO disequilibrium after ischemia/reperfusion (I/R) injury. Furthermore, administration of CS-B-NO efficiently attenuated cardiac damage and adverse cardiac remodeling, promoted repair of the heart, and ameliorated cardiac function, unlike a hydrogel that only released NO, in a mouse model of myocardial I/R injury. Mechanistically, regulation of the ROS/NO balance activated the antioxidant defense system and protected against oxidative stress induced by I/R injury via adaptive regulation of the Nrf2-Keap1 pathway. Inflammation is then reduced by inhibition of the activation of NF-𝜿B signaling. Collectively, these results show that this dual-function hydrogel may be a promising candidate for the protection of tissues and organs after I/R injury.

show abstract

Endothelium-Derived Nitric Oxide Regulates Postischemic Myocardial Oxygenation and Oxygen Consumption by Modulation of Mitochondrial Electron Transport

Cited by 114 publications

References 52 publications

Protein Tyrosine Nitration of the Flavin Subunit Is Associated with Oxidative Modification of Mitochondrial Complex II in the Post-ischemic Myocardium

Protein Tyrosine Nitration of the Flavin Subunit Is Associated with Oxidative Modification of Mitochondrial Complex II in the Post-ischemic Myocardium

Activation of Hsp90/NOS and increased NO generation does not impair mitochondrial respiratory chain by competitive binding at cytochrome C Oxidase in low oxygen concentrations

An Injectable Dual‐Function Hydrogel Protects Against Myocardial Ischemia/Reperfusion Injury by Modulating ROS/NO Disequilibrium

Contact Info

Product

Resources

About