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Mitogen-activated protein kinase p38alpha and retinal ischemic preconditioning
John C Dreixler1, Frank C Barone, Afzhal R Shaikh
1Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL, USA.
Experimental Eye Research
|July 28, 2009
Summary
Ischemic preconditioning (IPC) protects the retina by activating p38 mitogen-activated protein kinase (MAPK). This study shows p38 is crucial for IPC-induced neuroprotection, acting downstream of mitochondrial channels.
Area of Science:
- Neuroscience
- Cellular Biology
- Pharmacology
Background:
- Mitogen-activated protein kinase (MAP) p38 inhibition improves recovery after retinal ischemia.
- Ischemic preconditioning (IPC) normally attenuates p38 expression, suggesting a complex role.
Purpose of the Study:
- To investigate the hypothesis that p38 is required for IPC-induced ischemic tolerance.
- To elucidate the mechanisms of p38 involvement in IPC neuroprotection.
Main Methods:
- Rat retinas underwent IPC or direct ischemia.
- Functional (electroretinography) and histological assessments were performed after ischemia.
- p38alpha was inhibited using siRNA or SB203580; related pathways (mitochondrial KATP channels, adenosine receptors) were probed using diazoxide and receptor blockers.
Main Results:
- IPC increased phosphorylated p38 levels.
- Inhibition of p38alpha attenuated IPC's neuroprotective effects.
- Anisomycin-induced p38 activation mimicked IPC, while diazoxide-induced mimicry was blocked by p38alpha siRNA.
- Adenosine receptor blockade did not affect p38 phosphorylation post-IPC.
Conclusions:
- p38 mitogen-activated protein kinase (MAPK) is essential for the neuroprotective effects of ischemic preconditioning (IPC) in the retina.
- p38 acts downstream of mitochondrial KATP channels but not adenosine receptors in this neuroprotective pathway.
