title: cAMP-induced expression of ABCA1 is associated with MAP-kinase-pathway activation.
abstract: Several lines of evidence suggest that the ATP binding cassette A1 (ABCA1) is also involved in other degenerative processes such as brain neurodegeneration. Cholesterol and cAMP activate ABCA1 in a cell-specific manner. We employed a cell culture model of murine monocytes (P388) and neuroblastoma cells (N2A) and studied the differential induction of the ABCA1-gene product by modifying the cholesterol acceptor and by inhibition of the MAP-kinase pathway. Our study reveals a rise of ABCA1-expression in both N2A and P388 by cAMP. This increase is accompanied by a higher activation of the MAP-kinase-pathway. The inhibition of the MAP-kinase activation disrupts the stimulating effect of cAMP but increases the base line expression of ABCA1. Our data suggest a negative feedback between the MAP-kinase-system and ABCA1. We conclude that the interaction of the MAP-kinase pathway and the ABCA1 system might affect the function of neuronal and microglial cells in the brain.
authors.affiliation: University of Leipzig, Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Liebigstr. 27, D-40103 Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Witzlack
authors.forename: Tina
authors.initials: T
authors.lastname: Wenzeck
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Matthias
authors.initials: M
authors.lastname: Orth
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000242:Cyclic AMP; D020929:Mitogen-Activated Protein Kinase Kinases