Induction of protein kinase C substrates, Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP), by amyloid beta-protein in mouse BV-2 microglial cells.
Microglial activation by amyloid beta-protein in senile plaques contributes to neurodegeneration in Alzheimer disease. In BV-2 microglial cells, amyloid beta-protein 1-40 (Abeta 1-40) elicited a dose-dependent increase (3-4 fold) of Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP), two protein kinase C substrates implicated in membrane-cytoskeletal alterations underlying microglial adhesion, migration, secretion, and phagocytosis. Neither MARCKS nor MRP was induced by the amyloid fragment Abeta 25-35, although both Abeta 1-40 and Abeta 25-35 caused extensive aggregation of BV-2 cells. Interferon-gamma synergistically enhanced the induction by Abeta 1-40 of inducible nitric oxide synthase, but not MARCKS or MRP. Our results suggest that MARCKS and MRP may play important roles in microglia activated by amyloid peptides.
Murphy
Anne
A
Department of Pediatrics, Atlantic Research Centre, Dalhousie University, Room C-305 Clinical Research Centre, 5849 University Avenue, Halifax, NS B3H 4H7, Canada.
Sunohara
Janet R
JR
Sundaram
Meenakshi
M
Ridgway
Neale D
ND
McMaster
Christopher R
CR
Cook
Harold W
HW
Byers
David M
DM
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002148:Calmodulin-Binding Proteins; D002460:Cell Line; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010446:Peptide Fragments / Q000494:pharmacology; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D002148:Calmodulin-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000619711:Marcks protein, mouse; C512945:Marcksl1 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C