ArticleBiochimica et biophysica acta2012
Damage to mitochondrial complex I during cardiac ischemia reperfusion injury is reduced indirectly by anti-anginal drug ranolazine.
Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 83 citations in OpenAlex.
- Emerging therapy strategies for energy metabolism in acute myocardial infarction.Journal of translational medicine · 2025Review
- Retinal vascular dysfunction in the MthfrAlzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Investigating the potential of oxidative stress-related gene as predictive markers in idiopathic pulmonary fibrosis.Scientific reports · 2025Article
- Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency.Cell death discovery · 2025Article
- Data-Independent Acquisition Proteomics and N-Terminomics Methods Reveal Alterations in Mitochondrial Function and Metabolism in Ischemic-Reperfused Hearts.Journal of proteome research · 2024Article
- Status of Mitochondrial Oxidative Phosphorylation during the Development of Heart Failure.Antioxidants (Basel, Switzerland) · 2023Review
- Loss of PI3Kα Mediates Protection From Myocardial Ischemia-Reperfusion Injury Linked to Preserved Mitochondrial Function.Journal of the American Heart Association · 2023Article
- Administration of metformin rescues age-related vulnerability to ischemic insults through mitochondrial energy metabolism.Biochemical and biophysical research communications · 2023Article
- Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1.International journal of molecular sciences · 2022Article
- Hypothermia Prevents Cardiac Dysfunction during Acute Ischemia Reperfusion by Maintaining Mitochondrial Bioenergetics and by Promoting Hexokinase II Binding to Mitochondria.Oxidative medicine and cellular longevity · 2022Article
- No Direct Postconditioning Effect of Poloxamer 188 on Mitochondrial Function after Ischemia Reperfusion Injury in Rat Isolated Hearts.International journal of molecular sciences · 2021Article
- Mitochondrial respiratory supercomplexes in mammalian cells: structural versus functional role.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Metabolic Alterations Caused by Defective Cardiolipin Remodeling in Inherited Cardiomyopathies.Life (Basel, Switzerland) · 2020Review
- The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats.Communications biology · 2020Article
- Oxidative Stress-Responsive MicroRNAs in Heart Injury.International journal of molecular sciences · 2020Review
- Pentatricopeptide repeat protein DEK40 is required for mitochondrial function and kernel development in maize.Journal of experimental botany · 2019Article
- Inhibition of the ubiquitous calpains protects complex I activity and enables improved mitophagy in the heart following ischemia-reperfusion.American journal of physiology. Cell physiology · 2019Article
- Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies.International journal of molecular sciences · 2019Review
- Deactivation of mitochondrial complex I after hypoxia-ischemia in the immature brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- The role of cardiolipin concentration and acyl chain composition on mitochondrial inner membrane molecular organization and function.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ranolazine, an anti-anginal drug, is a late Na(+) channel current blocker that is also believed to attenuate fatty acid oxidation and mitochondrial respiratory complex I activity, especially during ischemia. In this study, we investigated if ranolazine's protective effect against cardiac ischemia/reperfusion (IR) injury is mediated at the mitochondrial level and specifically if respiratory complex I (NADH Ubiquinone oxidoreductase) function is protected. We treated isolated and perfused guinea pig hearts with ranolazine just before 30 min ischemia and then isolated cardiac mitochondria at the end of 30 min ischemia and/or 30 min ischemia followed by 10 min reperfusion. We utilized spectrophotometric and histochemical techniques to assay complex I activity, Western blot analysis for complex I subunit NDUFA9, electron paramagnetic resonance for activity of complex I Fe-S clusters, enzyme linked immuno sorbent assay (ELISA) for determination of protein acetylation, native gel histochemical staining for respiratory supercomplex assemblies, and high pressure liquid chromatography for cardiolipin integrity; cardiac function was measured during IR. Ranolazine treated hearts showed higher complex I activity and greater detectable complex I protein levels compared to untreated IR hearts. Ranolazine treatment also led to more normalized electron transfer via Fe-S centers, supercomplex assembly and cardiolipin integrity. These improvements in complex I structure and function with ranolazine were associated with improved cardiac function after IR. However, these protective effects of ranolazine are not mediated by a direct action on mitochondria, but rather indirectly via cytosolic mechanisms that lead to less oxidation and better structural integrity of complex I.
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