Functional analysis and its application of a G-protein coupled receptor, whose ligands are oxidized free fatty acids
| Project/Area Number |
18390082
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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 |
General medical chemistry
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| Research Institution | Gunma University |
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Principal Investigator |
IZUMI Takashi Gunma University, Graduate School of medicine, Professor (70232361)
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| Co-Investigator(Kenkyū-buntansha) |
TATEI Kazuaki Gunma University, Graduate School of medicine, Associate Professor (00192633)
OBINATA Hideru Gunma University, Graduate School of medicine, Assistant Professor (50332557)
KISHI Mikiko Gunma University, Graduate School of medicine, Assistant Professor (90396630)
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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 |
¥16,030,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Bioactive lipid / G-protein coupled receptor / Oxidized free fatty acid / Oxidized linoleic acid / DNA damage / Stress response / Keratinocyte / Gタンパク質共役型受容体 |
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| Research Abstract |
A purpose of this study was to clarify the physiological and pathological functions of a G-protein coupled receptor called G2A, and was to investigate the basic aspects of G2A signaling to establish new diagnosis / therapy. G2A is a receptor which ligands are oxidative flee fatty acids such as 9-HODE and 11-HETE derived from linoleic acid or arachidonic acid, respectively. It was reported that G2Awas induced by various DNA damage stimulation and its stimulation causes arrest of cell cycle. However, the physiological function of G2Awas unidentified.
As skin is routinely and pathologically exposed to many oxidative stresses such as UV radiation, chemical agents, and inflammation that might induce both G2A expression and production of G2A ligands, we examined G2A fraction in human keratinocytes. G2A was expressed in human epidermis and normal human epidermal keratinocytes (NHEK). 9-HODE evoked intracellular calcium mobilization, and secretion of cytokines including IL-6, IL-8, and GM-CSF in NHEK cells. These responses became prominent in HaCaT cells, an immortalized human keratinocyte cell line, by overexpression of G2A. 9-HODE further inhibited proliferation of NHEK cells by suppressing DNA synthesis and arresting the cell cycle in the G0/1-phase, and down-regulation of G2A expression by small interfering RNA caused suppression of 9-HODE-induced effects on proliferation of NHEK cells 13-HODE, much weaker ligand of G2A, did not show any effects on either cytokine secretion and proliferation in NHEK cells. On the other hand, UVB and hydrogen peroxide induced G2A expression and caused oxidation of linoleate to produce 9-HODE in HaCaT cells.
These results suggest that 9-HODE-G2A signaling plays proinflammatory roles in skin under oxidative conditions.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] G2A plays proinflammatory roles in human keratinocytes under oxidative stress as a receptor for 9-hydroxyoctadecadienoic acid2008
Author(s)
Hattori, T., Obinata, H., Ogawa, A., Kishi, M., Tatei, K. Ishikawa, O. Izumi, T.
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Journal Title
J Investigative Dermatology 128
Pages: 1123-1133
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Proteomic analysis identifies proteins that continue to grow hepatic stem-like cells without differentiation2008
Author(s)
Saheki, T., Ito, H., Sekiguchi, A., Nishina, A. Sugiyama, T., Izumi,T. Koijma, I.
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Journal Title
Description
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[Journal Article] Genetic background conversion ameliorates semi-lethality and permits behavioral analyses in cystathionine β-synthase-deficient mice, an animal model for hyperhomocysteinemia2008
Author(s)
Akahoshi, N., Kobayashi, C., Ishizaki, Y., Izumi, T., Himi, T., Suematsu, M. Ishii, I.
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Journal Title
Human Molecular Genetics (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Purification and characterization of lysophospholipase D from rat brain2006
Author(s)
Sugimoto, S., Sugimoto, H., Aoyama, C., Aso, C., Mori, M., Izumi, T.
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Journal Title
Biochim Biophys Acta 1761
Pages: 1410-1418
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Oxidized free fatty acid-G2A signaling mediates alarm signal May, 12, under oxidative stress2007
Author(s)
Izumi, T., Obinata, H., Hattori, T., Ogawa, A., Chen, K., Barliana, M. I. Kishi, M., Tatei, K.
Organizer
3rd International Conference on Phospholipases A2 and Lipid Mediators
Place of Presentation
Sorrento, Italy
Description
「研究成果報告書概要(欧文)」より
Related Report
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