Exploring the regulation of the expression of ChAT and VAChT genes in NG108-15 cells: implication of PKA and PI3K signaling pathways.
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.
Castell
Xavier
X
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, 91198 Gif-sur-Yvette, Cedex, France. xavier.castell@nbcm.cnrs-gif.fr
Cheviron
Nathalie
N
Barnier
Jean-Vianney
JV
Diebler
Marie-Françoise
MF
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D002795:Choline O-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006825:Hybridomas; D007546:Isoquinolines / Q000494:pharmacology; D026901:Membrane Transport Proteins; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013449:Sulfonamides; D014407:Tumor Cells, Cultured; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D026901:Membrane Transport Proteins; D009025:Morpholines; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; C493460:Slc18a3 protein, mouse; C493461:Slc18a3 protein, rat; D013449:Sulfonamides; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003994:Bucladesine; D000242:Cyclic AMP; D002795:Choline O-Acetyltransferase; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide