Ischemic and pharmacological preconditioning in Girardi cells and C2C12 myotubes induce mitochondrial uncoupling
Autor: | Joy McCarthy, Lydia Lacerda, James J. Meiring, Jan Minners, Michael N. Sack, Derek M. Yellon |
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Rok vydání: | 2001 |
Předmět: |
medicine.medical_specialty
Adenosine Physiology Cell Survival Vasodilator Agents Ischemia Mitochondrion Biology Membrane Potentials Mice Adenosine Triphosphate Oxygen Consumption Internal medicine Diazoxide medicine Animals Humans Inner mitochondrial membrane Muscle Skeletal Cell Line Transformed Cardioprotection L-Lactate Dehydrogenase Intracellular Membranes medicine.disease Flow Cytometry Cytoprotection Molecular biology Mitochondria Endocrinology Ischemic Preconditioning Myocardial Ischemic preconditioning Cardiology and Cardiovascular Medicine Hydroxy Acids Decanoic Acids medicine.drug |
Zdroj: | Circulation research. 89(9) |
ISSN: | 1524-4571 |
Popis: | Pharmacological uncoupling of mitochondrial oxidation from phosphorylation promotes preconditioning-like cardioprotection in the isolated rat heart. We hypothesized that modest mitochondrial uncoupling may be a critical cellular event in orchestrating preconditioning. Human-derived Girardi cells and murine C2C12 skeletal myotubes were preconditioned using simulated ischemia, adenosine, and diazoxide. Cell viability after 6 hours of simulated ischemia was measured using lactate dehydrogenase release and propidium iodide uptake. Mitochondrial inner membrane potential (ΔΨm) was investigated by flow cytometry, cellular ATP by recombinant firefly-luciferase bioluminescence, and cellular oxygen consumption using oximetry. Preconditioning enhanced cell viability with attenuation of lactate dehydrogenase release (≥30%, P P P 6 cells, simulated ischemia 3.1±0.1, adenosine 3.1±0.3, diazoxide 2.6±0.2, P ATP -channel antagonist 5-hydroxydecanoate. The uncoupled phenotype in response to preconditioning was similarly observed in C2C12 myotubes. The present study suggests that modest mitochondrial uncoupling represents a unifying cellular response which may be important in directing preconditioning-mediated cytoprotection. |
Databáze: | OpenAIRE |
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