ArticleCardiovascular research2014
Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Effects of Dietary Nitrate Supplementation on Weightlifting Exercise Performance in Healthy Adults: A Systematic Review.Nutrients · 2020Pooled it
- Nitrite increases mitofusin-1 levels to inhibit vascular smooth muscle cell proliferation and prevent intimal hyperplasia.Redox biology · 2026Article
- PKA activation rescues myocardial injury elicited by silica nanoparticles through improving oxidative stress, mitochondrial health, and copper homeostasis.Materials today. Bio · 2026Article
- Single-Cell Transcriptomics of Human Acute Myocardial Infarction Reveals Oxidative Stress-Associated Cardiomyocyte Subpopulations and Candidate Predictive Signatures.Antioxidants (Basel, Switzerland) · 2025Article
- lncRNA Oip5-as1 inhibits excessive mitochondrial fission in myocardial ischemia/reperfusion injury by modulating DRP1 phosphorylation.Cellular & molecular biology letters · 2024Article
- Mitochondrial Kinase Signaling for Cardioprotection.International journal of molecular sciences · 2024Review
- Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer.Journal of translational medicine · 2023Review
- The Reactive Species Interactome in Red Blood Cells: Oxidants, Antioxidants, and Molecular Targets.Antioxidants (Basel, Switzerland) · 2023Article
- Mitochondrial quality control in cardiac ischemia/reperfusion injury: new insights into mechanisms and implications.Cell biology and toxicology · 2023Review
- Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation.Annals of translational medicine · 2022Article
- Current Understanding of the Pivotal Role of Mitochondrial Dynamics in Cardiovascular Diseases and Senescence.Frontiers in cardiovascular medicine · 2022Review
- Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury.Life (Basel, Switzerland) · 2021Review
- Nitric oxide signalling in kidney regulation and cardiometabolic health.Nature reviews. Nephrology · 2021Review
- Article
- Possible Effects of Beetroot Supplementation on Physical Performance Through Metabolic, Neuroendocrine, and Antioxidant Mechanisms: A Narrative Review of the Literature.Frontiers in nutrition · 2021Review
- Myoglobin promotes nitrite-dependent mitochondrial S-nitrosation to mediate cytoprotection after hypoxia/reoxygenation.Nitric oxide : biology and chemistry · 2020Article
- AMPK, Mitochondrial Function, and Cardiovascular Disease.International journal of molecular sciences · 2020Review
- Targeting mitochondrial fusion and fission proteins for cardioprotection.Journal of cellular and molecular medicine · 2020Review
- Nitrite attenuates mitochondrial impairment and vascular permeability induced by ischemia-reperfusion injury in the lung.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Neuroprotective Mitochondrial Remodeling by AKAP121/PKA Protects HT22 Cell from Glutamate-Induced Oxidative Stress.Molecular neurobiology · 2019Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
aimsNitrite (NO2(-)), a dietary constituent and nitric oxide (NO) oxidation product, mediates cardioprotection after ischaemia/reperfusion (I/R) in a number of animal models when administered during ischaemia or as a pre-conditioning agent hours to days prior to the ischaemic episode. When present during ischaemia, the reduction of nitrite to bioactive NO by deoxygenated haem proteins accounts for its protective effects. However, the mechanism of nitrite-induced pre-conditioning, a normoxic response which does not appear to require reduction of nitrite to NO, remains unexplored. METHODS AND
resultsUsing a model of hypoxia/reoxygenation (H/R) in cultured rat H9c2 cardiomyocytes, we demonstrate that a transient (30 min) normoxic nitrite treatment significantly attenuates cell death after a hypoxic episode initiated 1 h later. Mechanistically, this protection depends on the activation of protein kinase A, which phosphorylates and inhibits dynamin-related protein 1, the predominant regulator of mitochondrial fission. This results morphologically, in the promotion of mitochondrial fusion and functionally in the augmentation of mitochondrial membrane potential and superoxide production. We identify AMP kinase (AMPK) as a downstream target of the mitochondrial reactive oxygen species (ROS) generated and show that its oxidation and subsequent phosphorylation are essential for cytoprotection, as scavenging of ROS prevents AMPK activation and inhibits nitrite-mediated protection after H/R. The protein kinase A-dependent protection mediated by nitrite is reproduced in an intact isolated rat heart model of I/R.
conclusionsThese data are the first to demonstrate nitrite-dependent normoxic modulation of both mitochondrial morphology and function and reveal a novel signalling pathway responsible for nitrite-mediated cardioprotection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.