Analysis of Differenciation Activity of Microbial Glycolipids on Animal Cells
Project/Area Number |
11660070
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
応用微生物学・応用生物化学
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Research Institution | University of Tsukuba |
Principal Investigator |
NAKAHARA Tadaatsu Institute of Applied Biochemistry Professor, 応用生物化学系, 教授 (80011930)
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Project Period (FY) |
1999 – 2000
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Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
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Keywords | Microbial glycolipids / Succynoyl trehalose lipids / Mannosylerythritol lipids / Differentiation / Apoptosis / HL-60 cell / Mouse melanoma B16 cell / PC12 cell / ラット神経系細胞株PC12 / プロテインキナーゼC / サクシノイルトレハロースリピド / 白血病細胞株 |
Research Abstract |
We found that the microbial extracellular glycolipids, succinoyl trehalose lipids (STL) induced monocytic differentiation while mannosylerythritol lipids (MEL) induced granulocytic differentiation of HL-60 human leukemia cells. In order to assess the mechanism of HL-60 cell differentiation-induction by STL, we examined the effects of analogs of STL with different hydrophobic fatty acid moieties on the growth and differentiation of HL-60 cells. Our results indicated that the effects of STL and its analogs on HL-60 cells depended on the structure of the hydrophobic moiety of STL. We also showed that MEL was a potent inhibitor of the proliferation of mouse melanoma B16 cells. Flow-cytometric analysis of the cell cycle of MEL-treated B16 cells revealed the accumulation of cells in the sub-G0/G1 phase, which is hallmark of cells undergoing apoptosis. The activity of protein kinase C (PKC) was reduced in B16 cells treated with MEL at a concentration at which induced apoptosis. Furthermore, exposure of rat pherochromocytoma PC12 cells to MEL enhanced the activity of acetylcholinesterase and interrupted the cell cycle at the G1 phase, with resulting outgrowth of neurites and partial cellular differentiation. Our results suggest that MEL induces characteristics of neuronal differentiation in PC12 cells, with transactivation of the c-jun gene, via an ERK-related signal cascade that is partially overlapping the pathways activated in response to NGF.
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Report
(3 results)
Research Products
(9 results)
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[Publications] Sudo, T., Zhao, X., Wakamatsu, Y., Shibahara, M., Nomura, N., Nakahara, T., Suzuki, A., Kobayashi, Y., Jin, C., Murata, T.and Yokoyama, K.: "Induction of differenciation of human HL-60 promyelocytic leukemia cell line by succinoyl trehalose lipid."Cytotechnology. 33. 259-264 (2000)
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[Publications] Zhao, X., Geltinger, C., Murata, T., Nomura, N., Nakahara, T.and Yokoyama, K.: "Treatment of mouse melanoma B16 cells with phorbol 12-myristate 13-acetate counterparts mannosylerythritol lipid-induced growth arrest and apoptosis."Cyotechnology. 33. 123-130 (2000)
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[Publications] Wakamatsu, Y., Zhao, X., Jin, C., Day, N., Shibahara, M., Nomura, N., Nakahara, T., Murata, T.and Yokoyama K.: "Mannosylerythritol lipid induces characteristics of neuronal differentiation of PC12 cells through an ERK-related signal cascade."European J.Biochem.. 268. 374-383 (2001)
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Related Report
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