Dissection of the molecular mechanism of the novel neurotrophin-like effects of secretory phospholipase A_2
| Project/Area Number |
16580054
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ARIOKA Manabu The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (20242159)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | secretory phospholipase A_2 / neurotrophic factor / L-type Ca^<2+> channel / apoptosis / PC12 / cerebellar granule neuron / neurite outgrowth / Aspergillus oryzae / 神経突起伸張 |
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| Research Abstract |
We previously demonstrated that secretory phospholipase A_2 (sPLA_2) and lysophosphatidylcholine (LPC) exhibit neurotrophin-like neuritogenic activity in the rat pheochromocytoma cell line PC12. Furthermore, sPLA_2 and LPC rescued cerebellar granule neurons from apoptotic cell death induced by deprivation of depolarizing stimulus. In the current study, we further analyzed the mechanism whereby sPLA_2 displays neurite-inducing activity. Exogenously-added mammalian group X sPLA_2 (sPLA_2-X), but not group IB and IIA sPLA_2s, induced neuritogenesis, which correlated with the ability of sPLA_2-X to liberate LPC into the culture media. In accordance, blocking the effect of LPC by supplementation of bovine serum albumin or phospholipase B attenuated neuritogenesis by sPLA_2 or LPC. Overproduction or suppression of G2A, a G protein-coupled receptor involved in LPC signaling, resulted in the enhancement or reduction of neuritogenesis induced by sPLA_2 treatment. These results indicate that neu
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ritogenic effect of sPLA_2 is mediated by generation of LPC and subsequent activation of G2A.
In contrast to mammalian sPLA_2s, much less is known for the physiological function of microbial sPLA_2. We cloned and characterized spaA and spaB encoding putative sPLA_2s from a filamentous fungus Aspergillus oryzae. PLA_2 activity assays showed that recombinant SpaA and SpaB had different enzymatic characteristics. Western blot and immunofluorescence analyzes demonstrated that, while SpaA was mainly secreted to culture medium, SpaB was associated with the intracellular structures reminiscent of the endoplasmic reticulum and/or lipid body. The expression of spaA was induced in response to carbon starvation, oxidative stress and conidiation, while spaB was constitutively expressed at very low steady level and upregulated in the cold-stressed condition. spaA- and spaB-overexpressing strains showed poor-conidiation phenotype which was remarkable in the latter. Although no morphological abnormalities were found in spaA, spaB, and spaA/spaB disruptants, we found that conidia of spaA disruptant and hyphae of spaB disruptant became sensitive to oxidative stress. These results suggest that fungal sPLA_2s play roles in defense system to oxidative stress. Less
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Report
(3 results)
Research Products
(33 results)
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[Journal Article] SspA, an outer membrane protein, is highly induced under salt-stressed conditions and is essential for growth under salt-stressed aerobic conditions in Rhodobacter sphaeroides f.sp.denitrificans.2005
Author(s)
Tsuzuki, M., Xu, X., Sato, S., Abo, M., Arioka, M., Nakajima, H., Kitamoto, K., Okubo, A.
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Journal Title
Appl.Microbiol.Biotechnol. 68(2)
Pages: 242-250
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Neuronal expression and neuritogenic action of group X secreted phospholipase A_2.2005
Author(s)
Masuda, S., Murakami, M., Takanezawa, Y., Aoki, J., Arai, H., Ishikawa, Y., Ishii, T., Arioka, M., Kudo, I.
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Journal Title
J.Biol.Chem. 280(24)
Pages: 23203-23214
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Secretory phospholipases A_2 induce neurite outgrowth in PC12 cells through lysophosphatidylcholine generation and activation of G2A receptor.2005
Author(s)
Ikeno, Y., Konno, N., Cheon, S.-h., Bolchi, A., Ottonello, S., Kitamoto, K., Arioka, M.
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Journal Title
J.Biol.Chem. 280(30)
Pages: 28044-28052
Description
「研究成果報告書概要(欧文)」より
Related Report
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