The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Protein Kinase G Transmits the Cardioprotective Signal From Cytosol to Mitochondria
Abstract
Ischemic and pharmacological preconditioning can be triggered by an intracellular signaling pathway in which G i -coupled surface receptors activate a cascade including phosphatidylinositol 3-kinase, endothelial nitric oxide synthase, guanylyl cyclase, and protein kinase G (PKG). Activated PKG opens mitochondrial K ATP channels (mitoK ATP ) which increase production of reactive oxygen species. Steps between PKG and mitoK ATP opening are unknown. We describe effects of adding purified PKG and cGMP on K + transport in isolated mitochondria. Light scattering and respiration measurements indicate PKG induces opening of mitoK ATP similar to K ATP channel openers like diazoxide and cromakalim in heart, liver, and brain mitochondria. This effect was blocked by mitoK ATP inhibitors 5-hydroxydecanoate, tetraphenylphosphonium, and glibenclamide, PKG-selective inhibitor KT5823, and protein kinase C (PKC) inhibitors chelerythrine, Ro318220, and PKC-ε peptide antagonist εV 1-2 . MitoK ATP are opened by the PKC activator 12-phorbol 13-myristate acetate. We conclude PKG is the terminal cytosolic component of the trigger pathway; it transmits the cardioprotective signal from cytosol to inner mitochondrial membrane by a pathway that includes PKC-ε.
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“MitoSNO has been reported to be protective in mice with cardiomyocyte deficiency of protein kinase G18, indicating that the cardio-protection conferred by MitoSNO is not due to nonmitochondrial pathways that operate through cyclic GMP–protein kinase G signaling3,6”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [6]
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Cites
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Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and ɛPKC
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Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C
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The Mitochondrial K Channel as a Receptor for Potassium Channel Openers
Garlid, K., Pauček, P., Yarov-Yarovoy, V. M., Sun, X., & Schindler, P. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8796 · Cited by 445
Self-citationMitochondrial PKCε and MAPK Form Signaling Modules in the Murine Heart
Baines, C. P., Zhang, J., Wang, G.-W., Zheng, Y.-T., Xiu, J. X., Cardwell, E. M., Bolli, R., & Ping, P. (2002) · Circulation Research · doi:10.1161/01.res.0000012702.90501.8d · Cited by 429
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A Protein Kinase C Translocation Inhibitor as an Isozyme-selective Antagonist of Cardiac Function
Johnson, J. A., Gray, M. O., Chen, C., & Mochly‐Rosen, D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.40.24962 · Cited by 377
Modulation of Mitochondrial ATP-Dependent K+Channels by Protein Kinase C
Sato, T., O'Rourke, B. P., & Marbán, E. (1998) · Circulation Research · doi:10.1161/01.res.83.1.110 · Cited by 366
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Développement de stratégies naturelles de cardioprotection : Quel rôle pour la mitochondries ?
Boulghobra, D. (2021) · theses.fr (ABES) · doi:10.70675/72de819azc0ebz4134zb302zc979b24377d3
Li, Y., Ma, Y. Y., Chen, J., Zhang, B., & Zhao, P. (2026) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2026.2687714
Sturz, G. R. (2013) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/f22m-7g83
Ischémie-reperfusion myocardique — Préconditionnement
Tissier, R., Ghaleh, B., & Berdeaux, A. (2010) · Réanimation · doi:10.1007/s13546-010-0103-4
Cardioprotection à la phase aiguë de l'infarctus
Ghaboura, N. (2010) · OpenGrey (Institut de l'Information Scientifique et Technique)
Metadata
- Authors
- Costa, A. D. T., Garlid, K. D., West, I. C., Lincoln, T. M., Downey, J. M., Cohen, M. V., & Critz, S. D.
- Affiliations
- Portland State University (US)
- Venue
- Circulation Research
- Published
- 2005-08-19
- Volume
- 97
- Issue
- 4
- Pages
- 329-336
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2151589110
- Cited by
- 307
- References
- 44
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 15 · 2014: 15 · 2013: 20 · 2012: 14
- FWCI
- 22.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL20648, HL35673, HL-67842, R01HL050688, HL50688, R01HL020648, R01HL067842)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- protein kinase G, mitochondrial KATP channels, cardioprotection, preconditioning, cyclic GMP, protein kinase C epsilon, ischemia, reactive oxygen species, mitochondrial respiration, potassium transport, endothelial nitric oxide synthase, guanylate cyclase, phosphatidylinositol 3-kinase, signal transduction
- MeSH terms
- Adenosine Triphosphate, Animals, Brain, Cytosol, Cyclic GMP, Male, Mitochondria, Heart, Mitochondria, Liver, Oxygen Consumption, Protein Kinase C, Tetradecanoylphorbol Acetate, Tetraethylammonium Compounds, Potassium Channels, Signal Transduction, Rats, Wistar, Cyclic GMP-Dependent Protein Kinases, Ischemic Preconditioning, Myocardial, Rats
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