2013 Fiscal Year Final Research Report
New strategy for drug development of cerebral ischemia; zinc signal is a potential target
| Project/Area Number |
23590644
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied pharmacology
|
|---|
| Research Institution | Gifu Pharmaceutical University |
|---|
Principal Investigator |
HARA Hirokazu 岐阜薬科大学, 薬学部, 准教授 (30305495)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ADACHI Tetsuo 岐阜薬科大学, 薬学部, 教授 (40137063)
KAMIYA Tetsuro 岐阜薬科大学, 薬学部, 助教 (60453057)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Keywords | 亜鉛 / 脳梗塞 / 神経細胞死 / アポトーシス / スプライシング |
|---|
| Research Abstract |
There is increasing evidence that excessive zinc release from presynaptic terminals following cerebral ischemia induces neuronal cell death. It was reported that the blockade of free zinc by zinc chelators abolishes the neurodegeneration induced by cerebral ischemia. These findings support the concept that zinc is one of mediators of ischemic neuronal cell death. However, the mechanism is not fully understood. In this study, we addressed molecular mechanisms of zinc-induced neurotoxicity. We demonstrated here that zinc-induced apoptosis might be regulated, at least in part, through alterations in splicing pattern of pro-apoptotic factor Bim. To our knowledge, this is first report showing a novel function of zinc as a splicing regulator. In addition, we provided evidence that apomorphine, a dopamine receptor agonist, protects against zinc-induced neurotoxicity independently of dopamine receptors.
|
