Nitrite Confers Preconditioning and Cytoprotection After Ischemia/Reperfusion Injury Through the Modulation of Mitochondrial Function

Portella, Rafael de Lima; Bickta, Janelle; Shiva, Sruti

doi:10.1089/ars.2015.6260

Cited by 21 publications

(11 citation statements)

References 238 publications

(296 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This data suggests that the protective effect of the delayed phase of IP do no depend anymore on the protein nitrosylation, which in the acute phase of IP leads to preservation of mitochondrial energetics, reduction of cytosolic Ca 2+ (Sun et al, 2007) and inhibition of the harmful ROS production (Chouchani et al, 2013; de Lima Portella et al, 2015). As early as 3 h post-IP, we observed a decrease in levels of 3-nitroTyr (Figure 3D)—the marker of NO-dependent oxidative stress (Mohiuddin et al, 2006).…”

Section: Discussionmentioning

confidence: 95%

Molecular Bases of Brain Preconditioning

et al. 2017

View full text Add to dashboard Cite

Preconditioning of the brain induces tolerance to the damaging effects of ischemia and prevents cell death in ischemic penumbra. The development of this phenomenon is mediated by mitochondrial adenosine triphosphate-sensitive potassium (KATP+) channels and nitric oxide signaling (NO). The aim of this study was to investigate the dynamics of molecular changes in mitochondria after ischemic preconditioning (IP) and the effect of pharmacological preconditioning (PhP) with the KATP+-channels opener diazoxide on NO levels after ischemic stroke in rats. Immunofluorescence-histochemistry and laser-confocal microscopy were applied to evaluate the cortical expression of electron transport chain enzymes, mitochondrial KATP+-channels, neuronal and inducible NO-synthases, as well as the dynamics of nitrosylation and nitration of proteins in rats during the early and delayed phases of IP. NO cerebral content was studied with electron paramagnetic resonance (EPR) spectroscopy using spin trapping. We found that 24 h after IP in rats, there is a two-fold decrease in expression of mitochondrial KATP+-channels (p = 0.012) in nervous tissue, a comparable increase in expression of cytochrome c oxidase (p = 0.008), and a decrease in intensity of protein S-nitrosylation and nitration (p = 0.0004 and p = 0.001, respectively). PhP led to a 56% reduction of free NO concentration 72 h after ischemic stroke simulation (p = 0.002). We attribute this result to the restructuring of tissue energy metabolism, namely the provision of increased catalytic sites to mitochondria and the increased elimination of NO, which prevents a decrease in cell sensitivity to oxygen during subsequent periods of severe ischemia.

show abstract

Section: Discussionmentioning

confidence: 95%

Molecular Bases of Brain Preconditioning

et al. 2017

View full text Add to dashboard Cite

show abstract

“…As high mitochondrial content is also a shared property of red muscle and cardiomyocytes, mitochondria could be involved in elevating intracellular nitrite concentration during deep hypoxia. Sequestering of nitrite inside mitochondria would be much in line with the fact that the cytoprotective effects of nitrite are largely directed at the mitochondria (Halestrap, 2004;Walters et al, 2012;de Lima Portella et al, 2015). In the mitochondria, nitrite S-nitrosates complex I, attenuating ROS generation during early reperfusion (Dezfulian et al, 2009;Chouchani et al, 2013), and nitrosylates complex IV, which inhibits oxygen consumption rates (HendgenCotta et al, 2008).…”

Section: Mb and No Metabolites In Red And White Musclementioning

confidence: 98%

The roles of tissue nitrate reductase activity and myoglobin in securing nitric oxide availability in deeply hypoxic crucian carp

Hansen

Lundberg

Filice

et al. 2016

Journal of Experimental Biology

View full text Add to dashboard Cite

In mammals, treatment with low doses of nitrite has a cytoprotective effect in ischemia/reperfusion events, as a result of nitric oxide formation and S-nitrosation of proteins. Interestingly, anoxia-tolerant lower vertebrates possess an intrinsic ability to increase intracellular nitrite concentration during anoxia in tissues with high myoglobin and mitochondria content, such as the heart. Here, we tested the hypothesis that red and white skeletal muscles develop different nitrite levels in crucian carp exposed to deep hypoxia and assessed whether this correlates with myoglobin concentration. We also tested whether liver, muscle and heart tissue possess nitrate reductase activity that supplies nitrite to the tissues during severe hypoxia. Crucian carp exposed to deep hypoxia (1

show abstract

“…Emerging evidence points to a central yet incompletely defined role for the first few minutes of reperfusion after ischemia [4]. On a subcellular level, the development and progression of myocardial injury in the early phase of reperfusion is mainly originated in mitochondria [5]. As a consequence of incomplete dioxygen reduction, mitochondria produce an excess of reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

Inorganic nitrite modulates miRNA signatures in acute myocardial in vivo ischemia/reperfusion

Hendgen‐Cotta

Messiha

Esfeld

et al. 2017

Free Radical Research

View full text Add to dashboard Cite

Acute myocardial infarction is the leading cause of mortality in the industrialized world. While it is essential to attempt an early reperfusion of ischemic myocardial territories, reperfusion itself adds damage to the heart, the ischemia-reperfusion (I/R) injury. Particularly the injury resulting from the very first minutes of reperfusion remains incompletely understood. MicroRNAs (miRNAs) are dynamic regulators in I/R injury. Nitric oxide ( NO) signaling, in turn, interacts with miRNA signaling. Our previous investigations showed that NO signaling in I/R could be modulated by nitrite. We therefore sought to investigate the role of miRNAs in nitrite cardioprotection with focus on the first few minutes of reperfusion. The study was conducted in mice in vivo with 30 min of ischemia and 5 min of reperfusion. Mice received a single-dose of nitrite or saline intracardially 5 min prior to reperfusion. We identified nine miRNAs to be up-regulated after 5 min of reperfusion. The up-regulation of almost half of those miRNAs (miR-125a-5p, miR-146b, miR-339-3p, miR-433) was inhibited by nitrite treatment, perpetuating baseline values. In silico analysis revealed the Irak-M gene to be a target of miR-146b and miR-339-3p. Correspondingly, a rise in Irak-M transcript and protein levels occurred by nitrite treatment within the early phase of reperfusion. The results demonstrate that already a very short phase of reperfusion is sufficient for significant dysregulation in cardiac miRNAs expression and that nitrite preserves baseline values of miRNAs in the scale of only a few minutes. These findings hint at a potential novel cardioprotective mechanism of nitrite signaling. ARTICLE HISTORY

show abstract

Nitrite Confers Preconditioning and Cytoprotection After Ischemia/Reperfusion Injury Through the Modulation of Mitochondrial Function

Abstract: These studies set the stage for current clinical trials testing the efficacy of nitrite to prevent warm and cold I/R injury.

Cited by 21 publications

References 238 publications

Molecular Bases of Brain Preconditioning

Molecular Bases of Brain Preconditioning

The roles of tissue nitrate reductase activity and myoglobin in securing nitric oxide availability in deeply hypoxic crucian carp

Inorganic nitrite modulates miRNA signatures in acute myocardial in vivo ischemia/reperfusion

Contact Info

Product

Resources

About