ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling.
While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETOH inhibition of NSC proliferation. Blocking the PLD signal by 1-butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway.
Fujita
Yuko
Y
Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Hiroyama
Masami
M
Sanbe
Atsushi
A
Yamauchi
Junji
J
Murase
Shoko
S
Tanoue
Akito
A
D020001:1-Butanol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010712:Phosphatidic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D010739:Phospholipase D / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D010712:Phosphatidic Acids; D000431:Ethanol; D004815:Epidermal Growth Factor; D020001:1-Butanol; D020929:Mitogen-Activated Protein Kinase Kinases; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1