© 2000 American Heart Association, Inc.
Integrative Physiology |
Adenosine A1 Receptor Induced Delayed Preconditioning in Rabbits
Induction of p38 Mitogen-Activated Protein Kinase Activation and Hsp27 Phosphorylation via a Tyrosine Kinase– and Protein Kinase C–Dependent Mechanism
From The Hatter Institute for Cardiovascular Studies, Department of Academic and Clinical Cardiology (A.D., D.M.Y.), and Centre for Cardiopulmonary Biochemistry (J.P.), University College London Hospitals and Medical School, and Royal Free Hospital School of Medicine (M.S.), London, UK.
Correspondence to Prof D.M. Yellon, The Hatter Institute for Cardiovascular Studies, Department of Academic and Clinical Cardiology, University College London Hospitals and Medical School, Grafton Way, London WC1E 6DB, UK. E-mail hatter-institute{at}ucl.ac.uk
Abstract—Transient adenosine A1 receptor (A1R) activation in rabbits induces delayed preconditioning against myocardial infarction 24 to 72 hours later. The cellular mechanisms downstream of A1R mediating this delayed cardioprotection have not been elucidated. This study examined the role of protein kinase C (PKC) and tyrosine kinases (TKs) in the signaling cascade mediating A1R-induced late preconditioning in rabbits. The small heat shock protein Hsp27 has been shown to confer cytoskeletal protection when in the phosphorylated state. We therefore also evaluated the potential role of the p38 mitogen-activated protein kinase (p38 MAPK) and Hsp27 as distal mediators of A1R-induced delayed preconditioning. Pharmacological preconditioning of rabbits with the selective A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 100 µg/kg) significantly reduced myocardial infarct size compared with control animals, after 30-minute regional ischemia/2-hour reperfusion in vivo 24 hours later (23.7±3.1 versus 43.0±4.1%; P<0.05). This delayed protection was abrogated by prior inhibition of either PKC with chelerythrine chloride (5 mg/kg) or of TKs with lavendustin A (1.3 mg/kg), suggesting that both PKC and TK are crucial for the development of delayed preconditioning after A1 receptor activation in the rabbit. Myocardial tissue extracts obtained 24 hours after CCPA treatment were analyzed for p38 MAPK catalytic activity using an in vitro kinase assay. This showed an almost 7-fold increase in p38 MAPK activity in myocardial samples pretreated with CCPA compared with control hearts. Two-dimensional gel electrophoresis revealed an increase in the phosphorylated isoforms of Hsp27 in hearts pretreated with CCPA compared with control hearts. Prior inhibition of either PKC or TK prevented the CCPA-induced increase in p38 MAPK activity and phosphorylation of Hsp27. This study identifies new components of the signaling mechanism of A1R-induced delayed preconditioning. Our results suggest an important role for both PKC and TK as mediators of late preconditioning against infarction after A1R activation and, although correlative, point to the p38 MAPK/Hsp27 pathway as a potential distal effector of this protection.
Key Words: adenosine • myocardial infarction • delayed preconditioning • protein kinase • heat shock protein
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|
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|
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|
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|
|
|
|
|
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