Differential activation of mitogen-activated protein kinases in acute, intermittent and chronic myocardial hypoxia in vivo
Abstract
Data di Pubblicazione:
2004
Citazione:
Differential activation of mitogen-activated protein kinases in acute, intermittent and chronic myocardial hypoxia in vivo / S. Morel, G. Milano, A. Corno, M. Samaja, L.K. Von Segesser, L. Kappenberger, C. Bonny, G. Vassalli. - In: EUROPEAN HEART JOURNAL. - ISSN 0195-668X. - 25:S(2004), pp. 374-375.
Abstract:
a risk factor for cardiovascular surgery. However, the underlying molecular mechanisms
are unknown. We investigated the role of MAPKs in CH compared with
acute (AH) and intermittent (IH) hypoxia. We used a novel type of normobaric
hypoxic chamber that permits to study the animals under true CH conditions (ie,
no cage opening for feeding and animal care). In contrast, most previous stud-ies involved daily opening of cages and, hence, results actually referred to IH (ie,
prolonged hypoxia with short daily periods of reoxygenation) rather than true CH.
Methods: Adult rats were subdivided into 4 groups: normoxia (N; O2 fraction=
21%), AH (O2 fraction=10% for 1h), CH and IH (n=6/group). CH and IH
rats were housed in a normobaric hypoxic chamber (O2 fraction =10%), but IH
rats were exposed to room air for 1h/day. After 2 weeks, CH and IH hearts were
excised and homogenized for extraction of cytosolic and nuclear proteins to determine
activation (phosphorylation) of c-Jun NH2-terminal kinases (JNK), extracellular
signal-regulated kinases (ERK), and p38 MAPK byWestern blot. JNK and
p38 MAPK activities were also determined by in vitro kinase assays. Mitochondria
were isolated to determine the subcellular distribution of cytochrome C and the
anti-apoptotic factor Bcl-2. Cardiomyocyte apoptosis was determined by TUNEL.
Results: AH was associated with significant (p<0.05) activation of JNK (3.4-fold)
and p38 MAPK (3.7-fold), IH with that of JNK (2.3-fold) and ERK (1.7-fold), and
CH with that of p38 MAPK alone (3.3-fold). JNK and p38 MAPK in vitro kinase assays
were consistent with these MAPK activation patterns. Cardiomyocyte apoptosis
was increased 2.2-fold in IH and 4-fold in CH. There were no differences in
the mitochondrial release of cytochrome C as well as expression and subcellular
distribution of Bcl-2 among groups.
Conclusions: AH, IH and CH are associated with differential MAPK activation in
rat hearts in vivo. p38 MAPK activation is associated with cardiomyocyte apoptosis
in CH, whereas JNK and ERK activation may be associated with cardioprotection
in IH. Results of ongoing in vivo experiments using selective inhibitors of
JNK and p38 MAPK in the intermittent and chronic hypoxia models will also be
presented to further characterize the effects of differential MAPK activation on
cardiomyocyte apoptosis under these conditions.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
S. Morel, G. Milano, A. Corno, M. Samaja, L.K. Von Segesser, L. Kappenberger, C. Bonny, G. Vassalli
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