Role of protein phosphatases in hypoxic preconditioning.
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| Abstract |
To find a protein kinase C (PKC)-independent preconditioning mechanism, hypoxic preconditioning (HP; i.e., 10-min anoxia and 10-min reoxygenation) was applied to isolated rat hearts before 60-min global ischemia. HP led to improved recovery of developed pressure and reduced end-diastolic pressure in the left ventricle during reperfusion. Protection was unaffected by the PKC inhibitor bisindolylmaleimide (BIM; 1 micromol/l). It was abolished by the inhibitor of protein phosphatases 1 and 2A cantharidin (20 or 5 micromol/l) and partially enhanced by the inhibitor of protein phosphatase 2A okadaic acid (5 nmol/l). In adult rat cardiomyocytes treated with BIM and exposed to 60-min simulated ischemia (anoxia, extracellular pH 6.4), HP led to attenuation of anoxic Na(+)/Ca(2+) overload and of hypercontracture, which developed on reoxygenation. This protection was prevented by treatment with cantharidin but not with okadaic acid. In conclusion, HP exerts PKC-independent protection on ischemic-reperfused rat hearts and cardiomyocytes. Protein phosphatase 1 seems a mediator of this protective mechanism.
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| Authors | Yury Ladilov, Hagen Maxeiner, Christopher Wolf, Claudia Schäfer, Karsten Meuter, H Michael Piper |
| Journal | American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 283 Issue 3 Pg. H1092-8 (Sep 2002) ISSN: 0363-6135 [Print] United States |
| PMID | 12181139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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