| Project/Area Number |
18390258
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Hiroshima University |
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Principal Investigator |
MATSUMOTO Masayasu Hiroshima University, Graduate school of Biomedical Sciences, Professor (20192346)
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| Co-Investigator(Kenkyū-buntansha) |
OHTSUKI Toshiho HIROSHIMA UNIVERSITY, HIROSHIMA UNIVERSITY Hospital, Associate Professor (20418792)
TAKAHASHI Tetsuya HIROSHIMA UNIVERSITY, HIROSHIMA UNIVERSITY Hospital, Assistant Professor (00435942)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥14,270,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2007: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2006: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | ischemic brain injury / neuronal stem cell / animal model |
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| Research Abstract |
Elucidation of the inna-cellular signal transduction during cerebral ischemia is essential for regenerative therapeutics against ischemic stroke induced brain damage. Hypoxia-inducible factor 1 (HIF1) is a ke transcription factor under hypoxic conditions, and those functional analyses are helpful far understanding the pathophysiology of cerebral ischemia
The activity of HIF-1a is regulated by two types of hydroxylases, prolyl-hydroxylase (PHD) and aspargynylhydroxylase factor inhibiting HIF-1a (FIH). Hydroxylation of HIF-1a by PHD and FIH causes proteasomal degradation and transcriptional inhibition of HIF-1a, respectively. The present study investigated the role of Siah-1 in the regulation of FIH abundance under normoxic conditions. Immunohistochemical analysis of the rat brains revealed that both Siah-1 and FIH were widely distributed in the central nervous system. FIH expression levels were increased in the presence of a proteasomal inhibitor MG132, suggesting that FIH is degraded by the ubiquitin用roteasome system. Immunoprecipitation assay and ubiquitination assay revealed that Siah-1 interacted with, and ubiquitinated FIH. Under normoxic conditions, Siah-1 facilitated degradation of FIH. On the other hand, when endogenous Siah-1 expression was suppressed using siRNA, FIH expression levels were increased, as compared to control.
We are plainning to examine Siah as a candidate target for the development of regenerative medicine.
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