on June 17, 2002
Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000022018.68965.6D
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Submitted on March 21, 2002
From the Divisions of Pediatric Surgery (P.R., Y.S., X.K., K.A.P., J.S., J.E.B.) and Cardiothoracic Surgery (J.S.T., S.B.L., R.D.J.), Medical College of Wisconsin, Milwaukee; and the Section of Cardiothoracic Surgery (J.S.T., S.B.L., K.M., R.D.J.), Children's Hospital of Wisconsin, Milwaukee. * To whom correspondence should be addressed. E-mail: jbaker{at}mcw.edu.
Background—Many infants who undergo heart surgery have a congenital cyanotic defect in which the heart is chronically perfused with hypoxic blood. However, the signaling pathways by which infant hearts adapt to chronic hypoxia and resist subsequent surgical ischemia is unknown. Method and Results—We determined the activation and translocation of protein kinase C (PKC) isoforms and mitogen activated protein kinases (MAP kinases) in 15 infants with cyanotic (SaO2<85%) or acyanotic (SaO2>95%) heart defects undergoing surgical repair and in 80 rabbits raised from birth in a hypoxic (SaO2<85%) or normoxic (SaO2>95%) environment. Tissues from infant human and rabbit hearts were processed for Western and in vitro kinase analysis. In human infants with cyanotic heart defects, PKC Conclusions—Infant human and rabbit hearts adapt to chronic hypoxia through activation of PKC
Revised on April 26, 2002
Accepted on May 1, 2002
Activation of Protein Kinases in Chronically Hypoxic Infant Human and Rabbit Hearts. Role in Cardioprotection
Parvaneh Rafiee PhD,
, p38 MAP kinase, and JUN kinase but not p42/44 MAP kinase were activated and translocated from the cytosolic to the particulate fraction compared with acyanotic heart defects. In rabbit infants there was a parallel response for PKC, p38 MAP kinase, and JUN kinase similar to humans. In infant rabbit hearts inhibition of PKC with chelerythrine, p38 MAP kinase, with SB203580 and JUN kinase with curcumin abolished the cardioprotective effects of chronic hypoxia but had no effects on normoxic hearts., p38 MAP kinase, and JUN kinase signal transduction pathways. These pathways may be responsible for cardioprotection in the chronically hypoxic infant rabbit heart.
Key words: hypoxia • ischemia • proteins • heart defects, congenital • heart diseases
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