Mek3
Recovery from the debilitating effects of ischaemic stroke is variable and
unpredictable. To maximize patient recovery, a greater understanding of the
molecular mechanisms involved in regulating both apoptosis and the repair
processes affecting neuronal protection, particularly in the penumbra region,
is desirable. We have previously shown, in human subjects, the increased
expression of several growth factors soon after stroke, together with
appearance of tyrosine phosphorylated proteins, in particular mitogen activated
protein (MAP) kinase (ERK1/2). In this paper, we demonstrate a relatively
short-lasting (< 12 h), but substantial increase in expression of
phosphorylated proteins, in particular, p-JNK (phosphorylated c-Jun N-terminal
kinase) and p-ERK1/2 in both the grey matter penumbra and infarcted tissue of
rats, following permanent middle cerebral artery occlusion. p-ERK1/2 was
associated with neurones and endothelial cells in the vicinity of the infarct
while p-JNK was mainly expressed in neurones. Expression of both p-MEK3/6 and
p-p38 MAP kinase was also increased in neurones and astroglia, within 1 h of infarction,
p-p38 remaining elevated and associated with neurones and in particular with
astroglia in the penumbra region for > 4 days. Evidence suggests that
short-term activation of these proteins may be detrimental to neuronal
survival, while their transient nature makes them unlikely to support
angiogenesis, revascularization and reperfusion over a period of days and
weeks. On the other hand, short-medium-term up-regulation of neuronal p-JNK,
p-c-Jun, p-Stat-1 and p-p38 might be a factor in the regulation of apoptosis.
Therapeutic manipulation of phosphorylation/activation of these and other
important signalling intermediates might form the basis of an appropriate
treatment to maximize revascularization and neuronal protection after ischaemic
stroke.
PMID: 12662322 [PubMed - indexed for MEDLINE]