ArticleCirculation2021
Oxidation of Protein Kinase A Regulatory Subunit PKARIα Protects Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Lysosomal-Triggered Calcium Release.
Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 40 citations in OpenAlex.
- A redox sensor in protein kinase A regulatory subunit Iα regulates vasodilation and protects against hypertension.Redox biology · 2026Article
- NMRK2-YAP-NADK axis preserves redox protection against myocardial ischemia/reperfusion injury.Redox biology · 2026Article
- Activation of TPC2 amplifies lysosome-mitochondria calcium transfer to regulate energetic stress responses.bioRxiv : the preprint server for biology · 2026Article
- Lysosomal CaCirculation. Arrhythmia and electrophysiology · 2025Article
- Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease.Life (Basel, Switzerland) · 2025Review
- Hyperammonemia increases the release of pathological extracellular vesicles from monocytes by impairing lysosomal function and autophagy through the TNFα-cAMP-PKA-LC3 pathway.Frontiers in immunology · 2025Article
- Optical theranostics in ischemic heart disease: from molecular insights to clinical translation.Theranostics · 2025Review
- Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development.Circulation · 2024Article
- Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control.Cardiovascular research · 2024Article
- Mitochondrial Kinase Signaling for Cardioprotection.International journal of molecular sciences · 2024Review
- The inotropic and arrhythmogenic effects of acutely increased late IFrontiers in cardiovascular medicine · 2024Article
- Mitochondrial Dynamics: Working with the Cytoskeleton and Intracellular Organelles to Mediate Mechanotransduction.Aging and disease · 2023Review
- Lysosomal calcium loading promotes spontaneous calcium release by potentiating ryanodine receptors.Biophysical journal · 2023Article
- Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Lysosomal CaPNAS nexus · 2023Article
- Lysosomal CaCell death discovery · 2023Article
- Aldehyde Dehydrogenase 2 Protects the Kidney from Ischemia-Reperfusion Injury by Suppressing the IOxidative medicine and cellular longevity · 2023Article
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- The old second messenger cAMP teams up with novel cell death mechanisms: potential translational therapeutical benefit for Alzheimer's disease and Parkinson's disease.Frontiers in physiology · 2023Review
- Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario.Frontiers in cardiovascular medicine · 2023Article
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18 authors at 9 institutions in 2 countries.
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Abstract
backgroundKinase oxidation is a critical signaling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, PKARIα (type-1 protein kinase A) can be reversibly oxidized, forming interprotein disulfide bonds in the holoenzyme complex. However, the effect of PKARIα disulfide formation on downstream signaling in the heart, particularly under states of oxidative stress such as ischemia and reperfusion (I/R), remains unexplored.
methodsAtrial tissue obtained from patients before and after cardiopulmonary bypass and reperfusion and left ventricular (LV) tissue from mice subjected to I/R or sham surgery were used to assess PKARIα disulfide formation by immunoblot. To determine the effect of disulfide formation on PKARIα catalytic activity and subcellular localization, live-cell fluorescence imaging and stimulated emission depletion super-resolution microscopy were performed in
resultsIn both humans and mice, myocardial PKARIα disulfide formation was found to be significantly increased (2-fold in humans,
conclusionsDisulfide modification targets PKARIα to the lysosome, where it acts as a gatekeeper for two-pore channel-mediated triggering of global calcium release. In the postischemic heart, this regulatory mechanism is critical for protection from extensive injury and offers a novel target for the design of cardioprotective therapeutics.
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