Transforming Growth Factor β1‐Regulated Cell Proliferation and Expression of Neural Cell Adhesion Molecule in B104 Neuroblastoma Cells

Journal of Neurochemistry - Tập 72 Số 6 - Trang 2286-2293 - 1999
Jia Luo1, Michael W. Miller
1Department of Psychiatry, University of Iowa College of Medicine, Iowa City 52242-1000, USA.

Tóm tắt

Abstract: The expression and activity of factors influencing early neuronal development are altered by ethanol. Such factors include growth factors, for example, platelet‐derived growth factor and basic fibroblast growth factor (for cell proliferation), and cell adhesion molecules (for neuronal migration). One agent, transforming growth factor β1 (TGFβ1), may affect both events. We tested the hypothesis that ethanol alters myriad TGFβ1‐mediated activities [i.e., cell proliferation and neural cell adhesion molecule (N‐CAM) expression] using B104 neuroblastoma cells. TGFβ1 inhibited the proliferation of B104 cells as evidenced by decreases in cell number and [3H]thymidine ([3H]dT) incorporation. TGFβ1 induced sustained activation of extracellular signal‐regulated kinases (ERKs), which are part of the family of mitogen‐activated protein kinases (MAPKs). Treatment with PD98059 (a MAPK kinase blocker) abolished TGFβ1‐regulated inhibition of [3H]dT incorporation. TGFβ1‐mediated growth inhibition was potentiated by ethanol exposure. Ethanol also produced prolonged activation of ERK, an effect that was partially eliminated by treatment with PD98059. On the other hand, TGFβ1 up‐regulated N‐CAM expression, and this up‐regulation was not affected by treatment with PD98059. Ethanol inhibited the TGFβ1‐induced up‐regulation of N‐CAM expression in a concentration‐dependent manner. Thus, TGFβ1 affects ERK‐dependent cell proliferation and ERK‐independent N‐CAM expression in B104 cells. Both activities are sensitive to ethanol and may underlie the ethanol‐induced alterations in the proliferation and migration of CNS neurons.

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Journal of Neurochemistry

Tập 72 Số 6

2286-2293

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