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Updated: Jul 12, 2026
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
The relationship between p38 mitogen-activated protein kinase and AMP-activated protein kinase during myocardial
Sebastien Jacquet1, Elham Zarrinpashneh, Audrey Chavey
1Cardiovascular Division, King's College London, St. Thomas' Hospital, London SEI 7EH, UK.
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.
Insights
AMP-activated protein kinase (AMPK) activation does not cause p38 mitogen-activated protein kinase (p38 MAPK) activation during myocardial ischemia. p38 MAPK activation during ischemia is independent of AMPK signaling.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Signaling
Background:
- p38 mitogen-activated protein kinase (p38 MAPK) and AMP-activated protein kinase (AMPK) are key regulators of myocardial ischemia response.
- Emerging evidence suggests a potential link where AMPK might mediate p38 MAPK activation during ischemia.
Purpose of the Study:
- To investigate whether AMP-activated protein kinase (AMPK) acts as the primary sensor for p38 mitogen-activated protein kinase (p38 MAPK) activation during myocardial ischemia.
Main Methods:
- Utilized genetic manipulation (isoform knockout and adenoviral expression) and pharmacological inhibition (compound C) to modulate AMPK activity in cardiac cells and isolated hearts.
- Assessed p38 MAPK activation under simulated and no-flow ischemia conditions.
Main Results:
- Temporal correlation observed between AMPK and p38 MAPK activity during ischemia in rat ventricular myocytes and mouse hearts.
- p38 MAPK activation remained unchanged in hearts lacking AMPKalpha1 or AMPKalpha2 isoforms.
- Modulating AMPKalpha1 activity or inhibiting AMPK pharmacologically did not affect p38 MAPK activation during ischemia.
Conclusions:
- Despite both kinases being activated during myocardial ischemia, p38 MAPK activation proceeds independently of AMPK signaling.
- AMPK is not the principal ischemia sensor responsible for p38 MAPK activation in the myocardium.
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