Record number :
Title of article :
Antimycin A induced cardioprotection is dependent on pre-ischemic p38-MAPK activation but independent of MKK3
Author/Authors :
Alamgir M.N. Kabir، نويسنده , , Xuebin Cao، نويسنده , , Diana A. Gorog، نويسنده , , Masaya Tanno، نويسنده , , Rehka Bassi، نويسنده , , Mohamed Bellahcene، نويسنده , , Roy A. Quinlan، نويسنده , , Roger J. Davis، نويسنده , , Richard A. Flavell، نويسنده , , Michael J. Shattock، نويسنده , , Michael S. Marber، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2005
Pages :
From page :
To page :
Abstract :
To examine the role of mitogen-activated protein kinase kinase 3 (MKK3) and p38 mitogen-activated protein kinase (p38-MAPK) in the cardioprotection afforded by antimycin A. Langendorff perfused murine hearts exposed to antimycin A or vehicle prior to global ischemia with p38-MAPK and HSP27 phosphorylation examined in the presence and absence of SB203580 or the presence (mkk3+/+) and absence (mkk3–/–) of MKK3. Infarct size was determined after 30 or 40 min of global ischemia and 2 h reperfusion. p38-MAPK dual phosphorylation in response to antimycin A was attenuated by co-administration of the antioxidant mercaptopropyonyl-glycine but unaffected by the absence of MKK3 or the presence of SB203580 at a concentration that inhibited the downstream phosphorylation of HSP27. Pre-ischemic exposure to antimycin A caused a significant reduction in subsequent infarction (I:R%) compared to vehicle on both the mkk3–/– and mkk3+/+ background (23.7 ± 2.9 and 22.8 ± 4.6 compared to 50.7 ± 4.0 and 49.6 ± 5.4 P = 0.001, respectively). In C57Bl6 mice, antimycin A prior to ischemia reduced infarct size compared to vehicle (22.8 ± 6.1 vs. 48.3 ± 5.2 P = 0.01, respectively), an effect abolished by coincident SB203580. The cardiac protection initiated by antimycin A is dependent on the activation of p38-MAPK which occurs, at least in part, in response to oxygen-derived free radicals. The mechanism of this protective form of p38-MAPK activation is independent of the upstream kinase MKK3 and does not involve autophosphorylation.
Keywords :
p38-MAPK , Antimycin A , hsp27 , SB203580
Journal title :
Journal of Molecular and Cellular Cardiology
Journal title :
Journal of Molecular and Cellular Cardiology
Serial Year :
Link To Document :