Brief reoxygenation episodes during chronic hypoxia enhance posthypoxic recovery of LV function: role of mitogen-activated protein kinase signaling pathways

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Serval ID
serval:BIB_E790C817037F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Brief reoxygenation episodes during chronic hypoxia enhance posthypoxic recovery of LV function: role of mitogen-activated protein kinase signaling pathways
Journal
Basic Research in Cardiology
Author(s)
Morel  S., Milano  G., Ludunge  K. M., Corno  A. F., Samaja  M., Fleury  S., Bonny  C., Kappenberger  L., von Segesser  L. K., Vassalli  G.
ISSN
0300-8428 (Print)
Publication state
Published
Issued date
07/2006
Volume
101
Number
4
Pages
336-45
Notes
Journal Article --- Old month value: Jul
Abstract
Children with congenital cyanotic heart defects have worse outcomes after surgical repair of their heart defects compared with noncyanotic ones. Institution of extracorporeal circulation in these children exposes the cyanotic heart to reoxygenation injury. Mitogen-activated protein kinase (MAPK) signaling cascades are major regulators of cardiomyocyte function in acute hypoxia and reoxygenation. However, their roles in chronic hypoxia are incompletely understood. We determined myocardial activation of the three major MAPKs, c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase-1/2 (ERK1/2), and p38-MAPK in adult rats exposed to hypoxia (FIO2=0.10) for varying periods of time. Myocardial function was analyzed in isolated perfused hearts. Acute hypoxia stimulated JNK and p38-MAPK activation. Chronic hypoxia (2 weeks) was associated with increased p38-MAPK (but not JNK) activation, increased apoptosis, and impaired posthypoxic recovery of LV function. Brief normoxic episodes (1 h/day) during chronic hypoxia abolished p38-MAPK activation, stimulated MEK-ERK1/2 activation modestly, and restored posthypoxic LV function. In vivo p38-MAPK inhibition by SB203580 or SB202190 in chronically hypoxic rats restored posthypoxic LV function. These results indicate that sustained hypoxemia maintains p38-MAPK in a chronically activated state that predisposes to myocardial impairment upon reoxygenation. Brief normoxic episodes during chronic hypoxia prevent p38-MAPK activation and restore posthypoxic recovery of myocardial function.
Keywords
Animals Anoxemia/blood/*physiopathology/therapy Apoptosis/physiology MAP Kinase Signaling System/*physiology Male Mitogen-Activated Protein Kinases/metabolism Oxygen/*physiology/therapeutic use Phosphorylation Rats Rats, Sprague-Dawley Time Factors *Ventricular Function, Left p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
Pubmed
Web of science
Open Access
Yes
Create date
15/02/2008 12:30
Last modification date
01/10/2019 7:20
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