- 作者: Yi-Hsuan Lee Chun-Hua Lin Li-Wen Hsu Ssu-Yao Hu Wen-Te Hsiao Yuan-Soon Ho
- 作者服務機構: Department of Physiology, Graduate Institute of Medical Sciences, Institute of Biotechnology, Taipei Medical University, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要:
We cultured a P19 mouse teratocarcinoma cell line and
induced its neuronal differentiation to study the func-
tion of ionotropic glutamate receptors (GluRs) in early
neuronal development. Immunocytochemical studies
showed 85% neuronal population at 5 days in vitro (DIV)
with microtubule-associated protein 2-positive staining.
Thirth percent and 50% of the cell expressed the α-ami-
no-3-hydroxy-5-methyl-4-isopropinonate (AMPA) recep-
tor subunit, GluR2/3, and the kainate (kainic acid; KA)
receptor subunit, GluR5/6/7, respectively. In Western blot
analysis, the temporal expression of GluR2/3 began to
appear at 3 DIV, whereas GluR5/6/7 was already ex-
pressed in the undifferentiated cells, P19-derived neu-
rons began to respond to glutamate, AMPA and KA, but
not to the metabotropic GluR agonist trans-1-aminocy-
clopentane-1,3-decarboxylic acid, by 5 DIV in terms of
increases in intracellular calcium and phospholipase C-
mediated poly-phosphoinositide turnover. Furthermore,
KA reduced cell death of P19-derived neurons in both
atmospheric and hypobaric conditions in a phospholi-
pase C-dependent mnner. The common AMPA/KA re-
ceptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione,
but not the AMPA receptor antagonist, 1,2,3,4-tetrahy-
dro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonam-
ide disodium, profoundly increased hypobaric insult-
induced neurotoxicity. In a flow cytometry study, the
nerve growth factor-mediated antiapoptotic effect was
facilitated by AMPA, with an inductioin of TrkA, but not
p75NTR expression. Therefore, AMPA and KA receptors
might mediate neurotrophic functioins to facilitate neuro-
trophic factor signaling to protect neurons against hyp-
oxic insult in early neuronal development. - 中文關鍵字: --
- 英文關鍵字: P19 cells. Glutamate receptor. Kainic acid. Hypoxia. Nerve growth factor