Signal transduction of ischemic preconditioning

Following 15 years of research, parts of the signal transduction cascade of ischemic preconditioning have been identified, and there is good agreement on the major endogenous triggers (adenosine, bradykinin, opioids, free radicals) involved in ischemic preconditioning, although, of course, the importance of different triggers varies among different species. Agreement exists also on the involvement of certain protein kinases, such as protein kinase C or protein tyrosine kinases, although the sequence of their activation (in series or parallel) appears to be once more species- and model-dependent. However, the importance of other elements of the downstream signal cascade, such as the MAP kinases and the ATP-dependent potassium channels, is still incompletely understood and the end-effector of preconditioning's protection is still unknown. Potential candidates of interest already exist (cytoskeleton or volume control), and the importance of novel proteins [291], such as desmin and villin, or kinases, such as Akt [291], in cardioprotection needs to be defined. A better understanding of the different elements within the signal transduction cascade and their hierarchic order is of utmost importance to potentially utilize the phenomenon of preconditioning in the clinical setting in the future.