ラット神経幹細胞の分化におけるギャップジャンクション細胞間コミュニケーション (GJIC) の役割 : p38 および ERK1/2 経路の関与(毒性学) Role of Gap Junctional Intercellular Communication (GJIC) through p38 and ERK1/2 Pathway in the Differentiation of Rat Neuronal Stem Cells(Toxicology)

ギャップジャンクションを介する細胞間コミュニケーション(GJIC)は中枢神経系の発達と分化に重要な役割を果たしている.本研究では, ラット脳より得た神経幹細胞および12-tetradecanoylphorbol-13-acetate (TPA)で誘導した神経幹細胞由来の細胞の分化過程におけるGJICの発現について検討した.神経幹細胞の分化過程の初期72時間以内ではCx43, Cx32の増加が見られた.神経幹細胞由来の細胞では, p38 MAPキナーゼを阻害するSB203580およびMEKを阻害するPD98059がTPAによるGJICの阻害からGJICを保護することが分かった.これらから, GJICは神経幹細胞の分化に重要な役割を果たしており, ERK7/2およびp38 MAPキナーゼシグナリング経路は機能的にラット神経幹細胞由来細胞のギャップジャンクションの調節に関与している可能性が考えられた.

Gap junctional intercellular communications (GJIC) contributes to neural function in development and differentiation of CNS. In this study, we have investigated the expression of GJIC during the differentiation of neuronal stem cells and 12-∅-tetradecanoylphorbol-13-acetate (TPA)-induced neuronal stem cell-derived cells from rat brain. During neuronal stem cell differentiation, expressions of Cx43 and 32 were increased for the duration of 72 hr, however the effect were decreased on the 7d. In the neuronal stem cell-derived cells, pretreatments with p38 MAP kinase inhibitor, SB203580, and MEK inhibitor, PD98059, could protect GJIC against TPA-induced inhibition of GJIC. Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells.