ケミカルバイオロジー研究グループ(終了)

PC-12細胞、SH-SY5Y細胞における神経分化誘導物質の探索

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概要

NGFのような神経栄養因子は、神経細胞の生き残りや、機能維持において重要な役割を持つ。これらの因子が減少すると、アルツハイマー病のような老人性痴呆を含む、さまざまな神経性疾患が起こるといわれている。このことは、NGFのような神経細胞の分化を誘導する物質はこれらの疾患に有用であることを示唆している。NGF、dBu-cAMP、スタウロスポリンによって分化が誘導され、神経突起を伸ばすことが知られているPC-12細胞、SH-SY5Y細胞を用いて、神経分化誘導物質をスクリーニングする。

(A)

(B)

(C)

Morphological changes of SH-SY5Y cells treated with epolactaene or dibutyryl cAMP.
The cells were cultured at 37 in 5 % CO2 humidified atmosphere in Basal Medium Eagle (BME) medium containing 10 % fetal bovine serum on plastic culture dishes. Photograph were obtained after 2 days cultivation with/without epolactaene or dibutyryl cAMP. (A), control; (B), with 10 ug/ml of epolactaene; (C), with 1 mM of dibutyryl cAMP. (Ref:2)

Day 1

Day 3

Control
NGF
MT-19
MT-20
Differentiation of normal PC12 cells induced by NGF or gamma-lactam-related compounds.
Cells were plated on poly-L-lysine-coated 24-well dishes at the density of 1000 cells per well. After 3 to 16 h, media were changed to fresh media containing 0.5 % FBS and NGF (100 ng/ml), MT-19 (1 ug/ml), or MT-20 (1 ug/ml). Cells were photographed after 1 nad 3 days of treatment. (Ref:1)

References:

  1. H. Kakeya, I. Takahashi, G. Okada, K. Isono, H. Osada.
    Epolactaene, a novel neuritogenic compound in human neuroblastoma cells, produced by a marine fungus.
    J. Antibiotics, 48, 733-735 (1995).

  2. M. Matsumoto, T. Sudo, M. Maruyama, H. Osada, M. Tsujimoto.
    Activation of p38 mitogen-activated protein kinase is crucial in osteoclastogenesis induced by tumor necrosis factor.
    FEBS Lett., 486, 23-28 (2000).

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