Role of protein phosphatases in hypoxic preconditioning

Physiologisches Institut, Justus-Liebig-Universität, D-35392 Giessen, Germany 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...

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Published inAmerican journal of physiology. Heart and circulatory physiology Vol. 283; no. 3; pp. H1092 - H1098
Main Authors Ladilov, Yury, Maxeiner, Hagen, Wolf, Christopher, Schafer, Claudia, Meuter, Karsten, Piper, H. Michael
Format Journal Article
LanguageEnglish
Published United States 01.09.2002
Subjects
Animals
Cantharidin - pharmacology
Enzyme Inhibitors - pharmacology
Hypoxia - metabolism
In Vitro Techniques
Indoles - pharmacology
Ischemic Preconditioning
Male
Maleimides - pharmacology
Muscle Fibers, Skeletal - enzymology
Myocardial Reperfusion Injury - metabolism
Myocardium - cytology
Myocardium - enzymology
Okadaic Acid - pharmacology
Phosphoprotein Phosphatases - metabolism
Protein Phosphatase 1
Protein Phosphatase 2
Rats
Rats, Wistar
Ventricular Pressure
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Summary:Physiologisches Institut, Justus-Liebig-Universität, D-35392 Giessen, Germany 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 µmol/l). It was abolished by the inhibitor of protein phosphatases 1 and 2A cantharidin (20 or 5 µmol/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. cellular calcium; heart function; ischemia; reperfusion
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00318.2001