Invited Symposium: Stroke/Cerebral Vasospasm
Cerebral vasospasm is featured by a prolonged contraction of cerebral arteries (17) and a proliferation in the vessel wall (28,29). The pathogenesis of cerebral vasospasm is not clear but probably relates to spasmogens released from blood clot such as hemolysate, oxyhemoglobin and adenosine triphosphate (ATP) or spasmogens released from vascular tissues such as endothelin.(18) Signal transduction pathways induced by these spasmogens are subjected to numerous investigations and several important signaling factors including phospholipase C (PLC), phospholipase A2 and protein kinase C (PKC) are identified. Recently, tyrosine kinase, which is involved in both vascular proliferation and contraction, has been shown to play a role in hemolysate-induced contraction of rabbit cerebral arteries.(15)
Mitogen-activated protein kinase (MAPK) is a family of serine/threonine protein kinases involved in cell growth, differentiation and transformation.(23) MAPK is activated by growth factors and by many G-protein coupled receptor (GPCR) agonists. GPCR agonists activate MAPK probably by firstly activation of PKC and tyrosine kinases. MAPK is presented in contractile phenotype of vascular smooth muscle cells,(2) and MAPK activity in peripheral vascular smooth muscle is enhanced during contraction.(1) The mechanism of MAPK-regulated contraction is probably related to the phosphorylation of caldesmon that is involved in prolonged smooth muscle contraction.(6) However, the role of MAPK in the regulation of contraction in cerebral arteries has not been studied.
We investigated the effect of hemolysate on MAPK phosphorylation and the effect of MAPK kinase inhibitor on hemolysate-induced contraction in rabbit basilar artery.
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|Zubkov, A.Y.; Ogihara, K.; Tumu, P.; Lewis, A.I.; (1998). Mitogen-Activated Protein Kinase Is Involved In The Pathogenesis Of Cerebral Vasospasm. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/zhang/zubkov0457/index.html|
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