ischaemic preconditioning of the human heart. - Leicester Research ...

institution o fcardiopu Imo nary bypass alone results in protection that mimicks that of'
ischaernic preconditioning is still elusive and clearly needs tiurther research.
Future Directions
The mechanism of protection induced by ischaernic preconditioning is yet to bc
completely understood. It would be appear that insult to the myocyte activates a
receptor-based trigger system which leads to activation of' PKC and MAPK and
mitochondrial KAIP channels which ultimately leads to protection. What remains
unclear is whether the activation of mitochondrial KAITchannels is up or downstream
of PKC and MAPK phosphorylation. Cellular stresses in many mammalian cell types
activate a distinct subset of the MAPK family of' enzymes. termed the Stress-
Activated Protein Kinases (SAPKs). The SAPKs are analogous to the Extracellularly
Regulated Kinase or ERK family of MAPKs which regulate predominantly the
growth and proliferation of cells in response to ffictors acting on tyrosine kinasc
receptors and G protein-coupled receptors. To date. two distinct groups of SAPKs
have been identified. The c-Jun N-terminal Kinases or JNKs and the p38 limily. The
mitogen activated protein kinases-p38 have been dernonstrated to he activated by
ischaemia/reperhision injury in the heart 1245.303.337.3481. The role of' the p38
MAPK signaling pathway in the early phase of' preconditioning seems to he
controversial. The two lines of studies performed to date have sought to determine (I)
whether preconditioning induces activation ofp38 MAPKs and (2) whether inhibition
of p38 MAPK abrogates the card ioprotect ive effect. I Intbrtunately. ix)th have yielded
conflicting results. Moreover, in man. the role of p38 MAPK signaling in
preconditioning and the final activation of the end-eflector(s) responsible t'()r cell
protection has yet to be elucidated.
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