Activation of protein kinases in chronically hypoxic infant human and rabbit hearts: role in cardioprotection. Circulation 2002 Jul 09;106(2):239-45
Date
07/10/2002Pubmed ID
12105165DOI
10.1161/01.cir.0000022018.68965.6dScopus ID
2-s2.0-0037047058 (requires institutional sign-in at Scopus site) 81 CitationsAbstract
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.
METHODS 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, PKCepsilon, 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 PKCepsilon, p38 MAP kinase, and JUN kinase similar to humans. In infant rabbit hearts inhibition of PKCepsilon 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.
CONCLUSIONS: Infant human and rabbit hearts adapt to chronic hypoxia through activation of PKCepsilon, p38 MAP kinase, and JUN kinase signal transduction pathways. These pathways may be responsible for cardioprotection in the chronically hypoxic infant rabbit heart.
Author List
Rafiee P, Shi Y, Kong X, Pritchard KA Jr, Tweddell JS, Litwin SB, Mussatto K, Jaquiss RD, Su J, Baker JEAuthors
John E. Baker PhD Professor in the Surgery department at Medical College of WisconsinKathleen Mussatto Ph.D. Associate Professor in the School of Nursing department at Milwaukee School of Engineering
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Activating Transcription Factor 2Active Transport, Cell Nucleus
Adaptation, Physiological
Animals
Cardiotonic Agents
Cell Nucleus
Chronic Disease
Cyclic AMP Response Element-Binding Protein
Enzyme Activation
Female
Heart Atria
Heart Defects, Congenital
Heart Ventricles
Humans
Hypoxia
Infant
Infant, Newborn
Male
Mitogen-Activated Protein Kinases
Myocardial Ischemia
Myocardium
Organ Culture Techniques
Phosphorylation
Protein Kinase C
Rabbits
Transcription Factors
