Exploring the regulation of the expression of ChAT and VAChT genes in NG108-15 cells: Implication of PKA and PI3K signaling pathways

被引:22
作者
Castell, X [1 ]
Cheviron, N [1 ]
Barnier, JV [1 ]
Diebler, MF [1 ]
机构
[1] CNRS, Neurobiol Cellulaire & Mol Lab, F-91198 Gif Sur Yvette, France
关键词
ChAT; VAChT; cholinergic locus; PKA; PI3K; muscarinic receptors;
D O I
10.1023/A:1022829608540
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Involvement of different protein kinases regulated by cAMP and implication of muscarinic receptors in the regulation of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) mRNA levels and ChAT activity has been studied in NG108-15 cells. Dibutyryl cAMP enhanced both ChAT and VAChT mRNA levels and stimulated ChAT activity. Muscarinic stimulation or inhibition did not change ChAT activity or the receptor subtype mRNA pattern. MEK1/2 did not affect the regulation of ChAT and VAChT mRNA levels. However, PKA plays a major role in regulating ChAT and VAChT mRNA levels, because H89 decreased both. Strikingly, inhibition of PI3K by LY294002 had two opposite effects: ChAT mRNA level was decreased and VAChT mRNA level was increased. Such a result consolidates the observation that ChAT and VAChT genes, despite their unusual organization in a single "cholinergic locus," can be differentially or synergistically regulated, depending on the activated signaling pathways.
引用
收藏
页码:557 / 564
页数:8
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