2011 Fiscal Year Final Research Report
Differential contribution of individual receptor subunits of N-methyl-d-aspartate to ischemic neuronal damage.
| Project/Area Number |
21591081
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
SASAKI Tsutomu 大阪大学, 医学部附属病院, 助教 (20534879)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Kazuo 大阪大学, 医学系・研究科, 准教授 (70301257)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Keywords | NMDA受容体 / NR2A / NR2B / TORC1/ CRTC1 / SIK2 / CREB |
|---|
| Research Abstract |
The cAMP responsive element-binding protein(CREB) functions in a broad array of biological and pathophysiological processes. We found that salt-inducible kinase 2(SIK2) was abundantly expressed in neurons and suppressed CREB-mediated gene expression after oxygen-glucose deprivation(OGD). OGD induced the degradation of SIK2 protein concomitantly with the dephosphorylation of the CREB-specific coactivator transducer of regulated CREB activity 1(TORC1), resulting in the activation of CREB and its downstream gene targets. Ca(2+)/ calmodulin-dependent protein kinase I/ IV are capable of phosphorylating SIK2 at Thr484, resulting in SIK2 degradation in cortical neurons. Neuronal survival after OGD was significantly increased in neurons isolated from sik2(-/-) mice, and ischemic neuronal injury was significantly reduced in the brains of sik2(-/-) mice subjected to transient focal ischemia. These findings suggest that SIK2 plays critical roles in neuronal survival, is modulated by CaMK I/ IV, and regulates CREB via TORC1.
|
-
[Journal Article] SIK2 is a new key regulator for neuronal survival after ischemia through TORC1-CREB2011
Author(s)
Sasaki T, Takemori H, Yagita Y, Terasaki Y, Uebi T, Horike N, Takagi H, Susumu T, Teraoka H, Kusano K, Hatano O, Oyama N, Sugiyama Y, Sakoda S, Kitagawa K.
-
Journal Title
Neuron
Volume: 13 ; 69(1)
Pages: 106-19
URL
Peer Reviewed
-
[Journal Article] A Potent Inhibitor of SIK2, 3, 3', 7-Trihydroxy-4'-Methoxyflavon(4'-O-Methylfisetin), Promotes Melanogenesis in B16F10 Melanoma Cells2011
Author(s)
Kumagai A, Horike N, Satoh Y, Uebi T, Sasaki T, Itoh Y, Hirata Y, Uchio-Yamada K, Kitagawa K, Uesato S, Kawahara H, Takemori H, Nagaoka Y
-
Journal Title
PLoS ONE
Volume: 6
Pages: 26148
DOI
Peer Reviewed
-
-
-
[Journal Article] Downregulation of SIK2 expression promotes the melanogenic program in mice2010
Author(s)
Horike N, Kumagai A, Shimono Y, Onishi T, Itoh Y, Sasaki T, Kitagawa K, Hatano O, Takagi H, Susumu T, Teraoka H, Kusano K, Nagaoka Y, Kawahara H, Takemori H.
-
Journal Title
Pigment Cell Melanoma Res
Volume: 23(6)
Pages: 809-19
DOI
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
