Exposure of rats to intermittent hypoxia determines different responses at tissue and cell level. Heart mainly undergoes the effects of hypoxic injury and its response is determined both by the relationship between oxygen supply and demand and by its functional state. Since molecular mechanisms mediate cells sensing and response to low O(2) concentration, here we explore the role played by Protein Kinase C alpha (PKC alpha) in the signal transduction mechanisms leading to the occurrence of morphological responses in rat neonatal, young and old heart subjected to intermittent hypoxia. Along with a key role for hypoxia inducible factor and vascular endothelial growth factor in the occurrence of continuous state of dynamic adaptation of vasculature, PKC alpha presumably phosphorylates IkBalpha in rat normoxic and hypoxic neonatal hearts, supporting the hypothesis of a rescue strategy carried out against hypoxia, together with an hypertrophic response. In hypoxic young heart PKC alpha activation, paralleled by sustained Bax homodimerization and caspase-3 activation, along with reduced p-IKBalpha and Inhibiting Apoptosis Protein (IAP) expression, suggests that the young early and deeply undergoes the effects of lowered oxygen tension. In addition, since no modifications concerning PKC alpha driven signalling system are evidenced in both the experimental conditions, we suggest an oxygen impaired sensing during ageing.

Molecular and morphological modifications occurring in rat heart exposed to intermittent hypoxia: role for protein kinase C alpha.

CATALDI, Amelia;BIANCHI, Giuseppina;SABATINI, NADIA;CENTURIONE, Lucia;DI GIULIO, Camillo;ANTONUCCI, Adriano
2004

Abstract

Exposure of rats to intermittent hypoxia determines different responses at tissue and cell level. Heart mainly undergoes the effects of hypoxic injury and its response is determined both by the relationship between oxygen supply and demand and by its functional state. Since molecular mechanisms mediate cells sensing and response to low O(2) concentration, here we explore the role played by Protein Kinase C alpha (PKC alpha) in the signal transduction mechanisms leading to the occurrence of morphological responses in rat neonatal, young and old heart subjected to intermittent hypoxia. Along with a key role for hypoxia inducible factor and vascular endothelial growth factor in the occurrence of continuous state of dynamic adaptation of vasculature, PKC alpha presumably phosphorylates IkBalpha in rat normoxic and hypoxic neonatal hearts, supporting the hypothesis of a rescue strategy carried out against hypoxia, together with an hypertrophic response. In hypoxic young heart PKC alpha activation, paralleled by sustained Bax homodimerization and caspase-3 activation, along with reduced p-IKBalpha and Inhibiting Apoptosis Protein (IAP) expression, suggests that the young early and deeply undergoes the effects of lowered oxygen tension. In addition, since no modifications concerning PKC alpha driven signalling system are evidenced in both the experimental conditions, we suggest an oxygen impaired sensing during ageing.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/119785
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