cAMP-induced expression of ABCA1 is associated with MAP-kinase-pathway activation.
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.
Witzlack
Thomas
T
University of Leipzig, Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Liebigstr. 27, D-40103 Leipzig, Germany.
Wenzeck
Tina
T
Thiery
Joachim
J
Orth
Matthias
M
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*
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000242:Cyclic AMP; D020929:Mitogen-Activated Protein Kinase Kinases