Acclimation to Hypoxia in Mammals: Preconditioning


Ischemic preconditioning is a particularly important phenomenon in heart and brain and is defined by models of tissue protection whereby a brief mild ischemic episode protects a tissue from a later more severe ischemic insult. The molecular pathways that underlie this tissue protection are best understood in heart but, for late preconditioning in particular, the pathways in heart and brain appear very similar. KATP channels of the plasma membrane or the mitochondria play a role as an effector of tissue protection by responding to a variety of upstream triggers including adenosine receptor activation, NO generation and reactive oxygen species. Protein kinase C isoform specific activation has been implicated as part of a major signal transduction pathway for preconditioning that may in turn signal through a downstream ERK pathway. In the oxygen glucose deprivation model of neuronal preconditioning activation of the NMDA receptor, calcium influx and generation of NO leads to activation of the an alternative pathway for preconditioning; the Ras pathway. Thus alternative activators including adenosine receptor agonists, growth factors and reactive oxygen species, will elicit protection through downstream signaling pathways such as the Ras or PKC pathways. Recent studies on VEGF expression in brain illustrate how such protective signaling pathways may also translate their lasting functional effects through regulation of synthesis and release of neuroprotective growth factors.


Adenosine Receptor KATP Channel Ischemic Precondition Myocardial Stunning Ischemic Tolerance 
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