ROCK2 regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway

• Boku, Shuken

• Nakagawa, Shin

• Toda, Hiroyuki

• Kato, Akiko

• Takamura, Naoki

• Omiya, Yuki

• Inoue, Takeshi

• Koyama, Tsukasa

抄録

Increased neurogenesis by promoting proliferation of neural precursor cells in the adult dentate gyrus might be beneficial for the treatment of psychiatric disorders. Results demonstrate that bFGF is necessary for the proliferation of neural precursor cells and that the glycogen synthase kinase-3β (GSK-3β) and β-catenin pathway plays a role in it. However, the detailed mechanism of proliferation of neural precursor cells remains unclear. To elucidate that mechanism, we investigated the role of Rho-associated coiled-coil kinase (ROCK) in bFGF-induced proliferation using SH-SY5Y cells as a model of neural precursor-like cells. Y27632, a specific inhibitor of ROCK, decreased bFGF-induced proliferation. Lithium (Li), an inhibitor of GSK-3β, recovered Y27632-decreased proliferation and quercetin (Que), an inhibitor of β-catenin pathway, reversed the recovery effect of Li. Both nuclear β-catenin and cyclin D1 expression were altered by bFGF, Y27632, Li, and Que in parallel with the case of proliferation. Furthermore, bFGF inactivated GSK-3β through increasing the phosphorylation of Ser9 on GSK-3β, which is reversed by Y27632 through increased phosphorylation of Tyr216 on GSK-3β. ROCK has two subtypes: ROCK1 and ROCK2. Investigation with siRNA for ROCKs showed that ROCK2 is involved in bFGF-induced proliferation, but not ROCK1. These results suggest that ROCK2 might mediate bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway. Further investigation of detailed mechanisms regulating the ROCK2/GSK-3β/β-catenin pathway might engender the development of new therapeutic targets of psychiatric disorders.

収録刊行物

• Brain Research

  Brain Research 1492 7-17, 2013-01-25

  Elsevier B.V.

キーワード

• GSK-3β
• β-catein

詳細情報

• CRID: 1050282677904771712
• NII論文ID: 120005228253
• HANDLE: 2115/52135
• ISSN: 00068993
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles