Activation of protein kinases in chronically hypoxic infant human and rabbit hearts: Role in cardioprotection

Parvaneh Rafiee, Yang Shi, Xiangrong Kong, Kirkwood A. Pritchard, James S. Tweddell, S. Bert Litwin, Kathleen Mussatto, Robert D. Jaquiss, Jidong Su, John E. Baker

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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, PKCε, 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 PKCε, p38 MAP kinase, and JUN kinase similar to humans. In infant rabbit hearts inhibition of PKCεwith 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. Conclusions - Infant human and rabbit hearts adapt to chronic hypoxia through activation of PKCE, p38 MAP kinase, and JUN kinase signal transduction pathways. These pathways may be responsible for cardioprotection in the chronically hypoxic infant rabbit heart.

Original languageEnglish (US)
Pages (from-to)239-245
Number of pages7
Issue number2
StatePublished - Jul 9 2002


  • Congenital
  • Heart defects
  • Heart diseases
  • Hypoxia
  • Ischemia
  • Proteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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