Basic analysis of sphingolipid metabolising enzyme and its application to the diagnosis of hematological and neuronal diseases
| Project/Area Number |
16590453
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory medicine
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
TAKASHI Murate Nagoya University, Department of Heath, professor, 医学部, 教授 (30239537)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Tetsuhito Nagoya University, Department of Health, professor, 医学部, 教授 (40161913)
TAKAGI Akira Nagoya University, Department of Health, research associate, 医学部, 助手 (30135371)
SUZUKI Motoshi Nagoya University, Graduate School of Medical Sciences, associated professor, 大学院・医学系研究科, 講師 (80236017)
BANNO Yoshiko Gifu University, School of Medicine, assistant professor, 医学部, 助教授 (50116852)
NOZAWA Yoshinori Gifu international Institute of Biotechnology, chief, 所長 (10021362)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | sphingosine kinase 1 / gene expression / promoter analysis / nerve growth factor / Trk A receptor / Sp1 protein / Sp1 protein / anti human SPHK1 antibody / SPHK1 gene expression / neuronal apoptosis / all trans retinoic acid |
|---|
| Research Abstract |
Sphingosine kinase (SPHK) is known to exert an anti-apoptic role in various cells and cell lines. We previously reported that human brain is rich in SPHK1 (Murate et al. 2001). After showing a high expression of SPHK1 in rat brain, we examined the gene expression mechanism using an NGF-stimulated rat PC12 cells. With RT-PCR, we found that both rat brain and PC12 utilized exon 1d out of 6 untranslated 1^<st> exons. NGF induced an increase in SPHK enzyme activity and protein expression about double those in PC12 cells, while NGF-induced SPHK1 mRNA was three times higher than in the control. The minimal 5' promoter was determined, and TrkA specific inhibitor K252a inhibited the NGF-induced promoter activity of SPHK1. The truncation or mutation of putative transcription factor-binding motifs revealed that one Sp1 binding motif of the 5' region of exon 1d is prerequisite. EMSA confirmed the promoter analysis, indicating increased Sp1 protein binding to this motif after NGF treatment. Chromatin immuno-precipitation assay confirmed the binding of Sp1 and the promoter region in vivo. These results suggest the signal transduction pathway from NGF receptor TrkA to transcription factor Sp1 protein binding to the promoter Sp1-like motif in NGF-induced rat SPHK1 gene expression.
|
Report
(3 results)
Research Products
(19 results)
-
-
-
-
-
-
[Journal Article] Sphingosine kinase 1 is involved in dibutyryl cyclic AMP-induced granulocytic differentiation through the upregulation of extracellular signal-regulated kinase, but not p38 MAP kinase, in HL602005
Author(s)
Koda M, Murate T, Wang S, Ohguchi K, Sobue S, Ikeda M, Tamiya-Koizumi K, Igarashi Y, Nozawa Y, Banno Y.
-
Journal Title
Biochim Biophys Acta. 1733(2-3)
Pages: 101-110
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
[Journal Article] Transcription factor specificity protein 1 (Sp1) is the main regulator of nerve growth factor-induced sphingosine kinase 1 gene expression of the rat pheochromocytoma cell line, PC12.2005
Author(s)
Sobue S, Hagiwara K, Banno Y, Tamiya-Koizumt K, Suzuki M, Takagi A, Kojima T, Asano H, Nozawa Y, Murate T.
-
Journal Title
J Neurochem. 95(4)
Pages: 940-949
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
-
-
-
-
-
-
