The relationship between p38 mitogen-activated protein kinase and AMP-activated protein kinase during myocardial ischemia.
OBJECTIVE
p38 mitogen-activated protein kinase (p38 MAPK) and AMP-activated protein kinase (AMPK) are activated by, and influence sensitivity to, myocardial ischemia. Recently a number of studies have suggested that AMPK may participate in the activation of p38 MAPK. We therefore examined whether AMPK may be the principal "ischemia sensor" responsible for p38 MAPK activation during myocardial ischemia.


METHODS
We used a variety of approaches to alter AMPK activity during ischemia and studied the repercussions on p38 MAPK activation.


RESULTS
The activities of AMPK and p38 MAPK were temporally related in adult rat ventricular myocytes (ARVM) subjected to simulated ischemia and in isolated mouse hearts subjected to no-flow ischemia. However p38 MAPK activation was unaltered in mouse hearts lacking the predominant or minor myocardial isoforms, AMPKalpha2 or AMPKalpha1 respectively. Likewise, in ARVM, adenoviral-driven expression of the minor myocardial isoform AMPKalpha1, in a constitutively active or dominant negative form reducing AMPK activity, did not alter p38 MAPK activation under basal conditions or during simulated ischemia. Finally, pharmacological inhibition of AMPK during ischemia with compound C did not attenuate the coincident activation of p38 MAPK.


CONCLUSIONS
Although AMPK and p38 MAPK are both activated during myocardial ischemia, the activation of p38 MAPK occurs independently of AMPK.
Jacquet
Sebastien
S
Cardiovascular Division, King's College London, St. Thomas' Hospital, London SEI 7EH, UK.
Zarrinpashneh
Elham
E
Chavey
Audrey
A
Ginion
Audrey
A
Leclerc
Isabelle
I
Viollet
Benoit
B
Rutter
Guy A
GA
Bertrand
Luc
L
Marber
Michael S
MS
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin; C534978:Prkaa2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases