Cited by 307Cardiac Ischemia and ReperfusionMitochondrial Function and PathologyCardiac electrophysiology and arrhythmias

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Protein Kinase G Transmits the Cardioprotective Signal From Cytosol to Mitochondria

Costa, Alexandre D.T., Garlid, Keith D., West, Ian C., Lincoln, Thomas M., Downey, James M., Cohen, Michael V., Critz, Stuart D.·2005·Circulation Research

DOI 10.1161/01.res.0000178451.08719.5b

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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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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)
ORCID: Costa, Alexandre D.T.
Garlid, Keith D.
Lincoln, Thomas M.
Downey, James M.
Cohen, Michael V.
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2005-08-19
Volume: 97
Issue: 4
Pages: 329-336
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/01.res.0000178451.08719.5b
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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Protein Kinase G Transmits the Cardioprotective Signal From Cytosol to Mitochondria

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