Postischemic Function and Protein Kinase C Signal Transduction

Autor: Thomas Rohs, Steven F. Bolling, Anthony J Georges, Kenneth S. Kilgore
Rok vydání: 1998
Předmět:
Male
Myocardial Ischemia
Sodium Chloride
Potassium Chloride
Calcium Chloride
chemistry.chemical_compound
Cytosol
Medicine
Myocyte
Magnesium
Enzyme Inhibitors
Cardioplegic Solutions
Protein Kinase C
Nucleotides
Kinase
Nucleosides
Hydrogen-Ion Concentration
Phenanthridines
Isoenzymes
Ischemic Preconditioning
Myocardial
Lactates
Female
Rabbits
Pharmaceutical Vehicles
Cardiology and Cardiovascular Medicine
Acetylcholine
Signal Transduction
medicine.drug
Pulmonary and Respiratory Medicine
Agonist
medicine.medical_specialty
medicine.drug_class
Myocardial Reperfusion
Diglycerides
Alkaloids
GTP-Binding Proteins
Internal medicine
Animals
Dimethyl Sulfoxide
Protein kinase C
Benzophenanthridines
business.industry
Myocardium
Cell Membrane
Antagonist
Myocardial Contraction
Bicarbonates
Chelerythrine
Endocrinology
chemistry
Surgery
business
Zdroj: The Annals of Thoracic Surgery. 65:1680-1684
ISSN: 0003-4975
Popis: Background . The protective effects of myocardial preconditioning may occur by way of multiple mechanisms, with G-protein-mediated protein kinase C (PKC) translocation as a final common pathway. In this study we investigate the pharmacologic induction of preconditioning, by PKC translocation, using PKC agonists/antagonists to reveal its effects on contractile function after myocardial ischemia. Methods . Langendorff-perfused rabbit hearts received: (1) control; (2) dimethyl sulfoxide (vehicle); (3) acetylcholine (0.55 mmol/L; PKC agonist); (4) 1,2- s,n -dioctanoylglycerol (DOG; 22 mmol/L; PKC agonist); (5) chelerythrine (0.8 mmol/L; PKC antagonist); or (6) DOG–chelerythrine followed by a 2-hour ischemic period, using modified St. Thomas cardioplegia and a 45-minute reperfusion period. The period of ischemia was chosen so as to allow for improvement by appropriate agonists. To observe metabolic changes, tissue nucleotides and nucleosides were measured. Membrane and cytosolic fractions of PKC were determined by an anti-PKC antibody directed against the PKC δ isozyme. Lactate levels and myocardial pH were measured. Results . The PKC agonists DOG and acetylcholine showed the greatest recovery of developed pressure (68% ± 2%, 60% ± 9%, respectively). Although pH, lactate, and nucleotide levels were similar between groups at all times, myocyte PKC translocation demonstrated 25% of PKC δ isoforms on cell membrane sites during baseline, which shifted to 67% ± 17% with unprotected ischemia. DOG mimicked this shift with 58% ± 12% of PKC δ isoforms on membranes, which was also blocked by chelerythrine to 35% ± 7%. Conclusions . These data demonstrate that PKC translocation results in improved postischemic function, not by alteration of energetics or metabolism, and deserves further investigation.
Databáze: OpenAIRE
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