| Project/Area Number |
14380310
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH |
|---|
Principal Investigator |
KANAHO Yasunori TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, DEPARTMENT DIRECTOR, 東京都臨床医学総合研究所・専門参事(部長) (00214437)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ITOH Kouichi TOKUSHIMA BUNRI UNIVERSITY, FUCULTY OF PHARMACEUTICAL SCIENCES AT KGAWA CAMPUS, 香川薬学部, 教授 (30291149)
SASAKI Takehiko AKITA UNIVERSITY, SCHOOL OF MEDICINE, 21 CENTURY COE PROGRAM, INVESTIGATOR, 医学部・21世紀COEプログラム, 研究員 (50333365)
MAEHAMA Tomohiko TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, INVESTIGATOR, 研究員 (40322755)
WATANABE Hiroshi TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, INVESTIGATOR, 研究員 (80356261)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2003: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
|
|---|
| Keywords | Phospholipase D / Neurite / ERK / PC 12 cells / Cerebellar granule cells / NGF / Neuronal adhesion molecule / Signal transduction / 小脳顆粒細胞 / 軸索伸長 / 神経細胞接着分子 / 一級アルコール |
|---|
| Research Abstract |
Mammalian phospholipase D (PLD) is a novel signal transducing enzyme, which is believed to play roles in a wide variety of cell functions. Two mammalian PLD isozymes, PLD1 and PLD2,have been identified. Although activation mechanisms and physiological functions of PLD1 have been well documented, those of PLD2 still remain to be clarified. In the present study, we investigated whether PLD2 is involved in axonal outgrowth using PC12 cells and primary cultured cerebellar granule neurons.
(1)Phospholipase D2 Functions as a Downstream Signaling Molecule of MAP kinase Pathway in L1-Stimulated Neurite Outgrowth of Cerebellar Granule:
In the cerebellum of postnatal day 8 mice, PLD2 protein was abundantly expressed, while PLD1 was not detected. The L1-stimulated neurite outgrowth was inhibited by overexpression of lipase-deficient (LD) PLD2. Furthermore, it was found that L1 stimulation in CGNs increased PLD activity concomitantly with phosphorylation of extracellular signal-regulated kinase (ERK
… More
), both of which were inhibited by the MAP kinase-ERK kinase (MEK) inhibitor. These results provide evidence that PLD2 functions as a downstream signaling molecule of ERK to mediate the L1-dependent neurite outgrowth of CGNs, a mechanism that may be related to alcohol-related neurodevelopmental disorders.
(2)Essential Role of Phospholipase D2 Activation Downstream of ERK MAP Kinase in the Signaling Pathway of NGF-Stimulated Neurite Outgrowth in PC12 Cells:
Increased expression of wild type PLD2 (WT-PLD2), but not WT-PLD1,in a PC12 clonal cell line dramatically elongated neurites induced by NGF stimulation or transient expression of the active form of MAP kinase-ERK kinase (MEK-CA). In contrast, neurite elongation was inhibited by expression of LD-PLD2. Furthermore, the MEK inhibitor suppressed PLD2 activation and the hypertrophic neurite extension induced by NGF in PC12 cells inducibly expressing WT-PLD2. MEK-CA stimulated the activity of co-expressed PLD2. These results provide evidence that PLD2 functions as a downstream signaling molecule of ERK in the signaling pathway of the NGF-induced neurite outgrowth of PC 12 cells. Less
|
