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Altered gene expression in embolic stroke model with SMTP‐7 and t‐PA treatment
Author(s) -
Hashimoto Terumasa,
Shibata Keita,
Nobe Koji,
Hasumi Keiji,
Honda Kazuo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.842.8
Subject(s) - gene expression , proinflammatory cytokine , stroke (engine) , tissue plasminogen activator , medicine , ischemia , pharmacology , inflammation , gene , biology , biochemistry , mechanical engineering , engineering
We have reported that SMTP‐7, a novel fungal metabolite, has excellent therapeutic effect on cerebral infarction in embolic stroke model in mice. As functional mechanisms of this compound have not been fully elucidated, the gene expression of tissue plasminogen activator (t‐PA)‐ and SMTP‐7‐induced thrombolytic reperfusion was investigated using embolic stroke model in nice. Thrombotic occlusion was induced by local application of acetic acid to the right common carotid artery in the male mice. Microarray analysis was used to investigate the change in gene expression. 96 genes involved inflammatory response and cell death were screened in control mice. Fifty two and 86 genes out of 96 were recovered by treatment of t‐PA and SMTP‐7 at 1hr after ischemia respectively. In the case of t‐PA treatment at 3hr after ischemia, 30 genes out of 96 were upregulated as compared with control but SMTP‐7 hardly affected. The different gene expression between t‐PA‐treated and SMTP‐7‐treated group, including Lcn2, S100A8, Mmp9, Ncf2 and Ccl2 was confirmed by RT‐PCR. These observations suggest that broad therapeutic time window of SMTP‐7 attributes the suppressive effect on these proinflammatory gene expression after ischemia and reperfusion.