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.
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 infanthuman and rabbit hearts were processed for Western and in vitro kinase analysis. In humaninfants 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 rabbitinfants there was a parallel response for PKCepsilon, p38 MAP kinase, and JUN kinase similar to humans. In infantrabbit 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:Infanthuman 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 infantrabbit heart.
Authors: Martina J Klevstig; Irena Markova; Jana Burianova; Ludmila Kazdova; Michal Pravenec; Olga Novakova; Frantisek Novak Journal: Mol Cell Biochem Date: 2011-05-31 Impact factor: 3.396
Authors: Markéta Hlaváčková; Kristýna Kožichová; Jan Neckář; František Kolář; René J P Musters; František Novák; Olga Nováková Journal: Mol Cell Biochem Date: 2010-09-19 Impact factor: 3.396
Authors: John E Baker; Jidong Su; Anna Hsu; Yang Shi; Ming Zhao; Jennifer L Strande; Xiangping Fu; Hao Xu; Annie Eis; Richard Komorowski; Eric S Jensen; James S Tweddell; Parvaneh Rafiee; Garrett J Gross Journal: Cardiovasc Res Date: 2007-09-22 Impact factor: 10.787