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Ischemic preconditioning: from adenosine receptor to KATP channel.
M V Cohen1, C P Baines, J M Downey
1Department of Medicine, University of South Alabama, College of Medicine, Mobile 36688, USA. mcohen@usamail.usouthal.edu
Annual Review of Physiology
|June 9, 2000
Summary
Ischemic preconditioning protects the heart by activating a kinase cascade. This pathway involves protein kinase C, p38 MAPK, and HSP27, ultimately opening mitochondrial K+ channels to reduce heart tissue damage.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Ischemic preconditioning is a protective phenomenon against myocardial infarction.
- Understanding its mechanism could lead to new therapeutic strategies.
Purpose of the Study:
- To elucidate the molecular mechanism of ischemic preconditioning in the rabbit myocardium.
- To identify the key signaling molecules and pathways involved in cardioprotection.
Main Methods:
- Induction of brief ischemic preconditioning followed by prolonged ischemia in rabbit hearts.
- Analysis of signaling pathways including G proteins, phospholipases, protein kinase C, tyrosine kinase, p38 MAPK, and HSP27.
- Investigation of mitochondrial K+ channel activity.
Main Results:
- Preconditioning releases adenosine, bradykinin, opioids, and oxygen radicals.
- This triggers protein kinase C activation, initiating a kinase cascade involving tyrosine kinase and p38 MAPK.
- The cascade leads to HSP27 phosphorylation and opening of mitochondrial ATP-sensitive K+ channels, conferring protection.
Conclusions:
- Ischemic preconditioning involves a complex kinase cascade culminating in mitochondrial K+ channel opening.
- This pathway, involving protein kinase C, p38 MAPK, and HSP27, protects the myocardium from ischemic injury.
- Redundancies in the pathway may explain species-specific differences in preconditioning effects.