演題番号 : P1-b10
松尾 明典 / Akinori Matsuo:1 ベリエ ジャンピエール / Jean-Pierre Bellier:1 西村 正樹 / Masaki Nishimura:1 安原 治 / Osamu Yasuhara:1 齋藤 尚亮 / Naoaki Saito:2 木村 宏 / Hiroshi Kimura:1
1:滋賀医大・分子神経科学研 / Mol Neurosci Res Center, Shiga Univ of Medical Science, Otsu 2:神戸大学バイオシグナル研究センター / Biosignal Research Center, Kobe University, Kobe
Choline acetyltransferase (ChAT) synthesizes a major neurotransmitter acetylcholine (ACh) at cholinergic nerve terminals. However, ChAT bears nuclear localization signal (NLS) and is localized also in the nuclei of neural and non-neuronal cells. Nuclear ChAT might have a yet unidentified, pivotal function such as transcriptional regulation. In this study, we investigated the alteration of candidate gene transcription by ChAT. We chose high affinity choline transporter (CHT1) and vesicular acetylcholine transporter (VAChT) genes as candidates, which are functionally related to ChAT in ACh production. Using SH-SY5Y human neuroblastoma cells stably expressing wild-type human ChAT, we found that overexpressed ChAT enhanced the transcription of CHT1 gene but not of VAChT gene. In contrast, NLS-disrupted and catalytically inactive mutant ChATs could not induce CHT1 expression. Additionally, ChAT did not alter CHT1 expression in non-neuronal HEK293 cells. We also studied the effect of PI3K inhibitor on this induction. PI3K inhibitor did not reversed upregulation of CHT1 by ChAT, although partial reduction was observed. Our results suggest that ChAT activates transcription of selected target genes in neuronal cells. Both enzymatic activity and nuclear translocation of ChAT is required for the transcriptional enhancement. In this study, we demonstrated a possible function of intranuclear ChAT for the first time.