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

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

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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Crossref · 10.1161/01.res.0000178451.08719.5b

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  • MitoSNO cardioprotection is not due to nonmitochondrial cyclic GMP-protein kinase G pathways, because MitoSNO protected mice with cardiomyocyte protein kinase G deficiency.

    “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”

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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)
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 › Pathology and Forensic 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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