Activated MARCKS Signaling Pathway In MI

Background: The proteins of the MARCKS (myristoylated alanine-rich kinase substrate) family were first identified as prominent substrates of protein kinase C (PKC). Since then, these proteins have been implicated in the regulation of brain development. The expression and activation of MARKCS in brain ischemia have not been reported. Objective: The purpose of this study is to investigate the expression of MARCKS in brain ischemia. Furthermore, we have explored the role of granula 9601 on MARCKS signal transduction pathway in acute brain ischemia model.Methods:(1) The model was established by method of Kaneko. The role of granula 9601 was investigated, and Nimodipine was taken as control.(2) The stroke symptoms and signs scoring system are used to evaluate the animal model.(3) Microscope and electronic microscope were used to watch the ultra structure of mouse brain. (4) The expression pattern of these proteins was further analyzed for their distribution at cellular level by immunohistochemistry staining of the tissues. (5) Statistical analysis was performed with SPSS software version 10.0. The expression of MARCKS and p-MARCKS was analyzed by t test. P < 0.05 was considered to be statistically significant. Results:(1) We found that the score of the acute multi-cerebral infarction mouse reached its peak at day 3~4, and the score was decreased gradually after 7 days. (2) We found that the score of the acute multi-cerebral infarction mouse after treatment of granula 9601 was lower than that of the model with no treatment (P < 0.05),but no difference with that of the group after treatment of Nimodipine (P >0.05).(3) The pathology and ultra structure of the operated mouse was found with obvious alterations of ischemia, and we found that treatment with granula 9601 and Nimodipine could inhibit the change.(4) The expression of MARCKS and p-MARCKS protein in tissues of acute ischemia brain were elevated comparing with the normal and control group (P < 0.05), and the expression of the above two proteins were decreased after two weeks. (5) The expression of MARCKS and p-MARCKS were found decreased in ischemia brain tissues with treatment of granula 9601 and Nimodipine.Conclusion: (1) We found that the MI model had similar symptoms and morphological changes with clinical patients, and treatment with granula 9601 could inhibit the damage to the neuron.(2) The expression and activation of MARCKS and p-MARCKS were elevated in brain under the condition of acute ischemia, suggesting that overexpression of MARCKS transduction pathway might play an important role in brain ischemia.(3) The overexpression and activation of MARCKS and p-MARCKS were correlated with the score of symptoms and signs of nervous system, suggesting that the expression and activation of MARCKS and p-MARCKS were associated with severity of ischemia.(4) Treatment with granula 9601 could inhibit the expression and activation of MARCKS protein; MARCKS signal transduction pathway could be novel target for the treatment of acute ischemia.