Acetylcholine induces neurite outgrowth and modulates matrix metalloproteinase 2 and 9.
The matrix metalloproteinases (MMPs), responsible for the degradation of extracellular matrix (ECM) proteins, may regulate brain cellular functions. Choline acetyltransferase (ChAT) transfected murine neuroblastoma cell line N18TG2, that synthesize acetylcholine and show enhancement of several neurospecific markers (i.e., sinapsin I, voltage gated Na(+) channels, high affinity choline uptake) and fiber outgrowth, were studied for the MMP regulation during neuronal differentiation. Zymography of N18TG2 culture medium revealed no gelatinolytic activity, whereas after carbachol treatment of cells both MMP-9 and activated MMP-2 forms were detected. ChAT-transfected clone culture medium contains three MMP forms at 230, 92, and 66kDa. Carbachol treatment increased MMP-2 and MMP-9 gene expression in N18TG2 cells and higher levels for both genes were also observed in ChAT transfected cells. The data are consistent with the hypothesis that acetylcholine brings about the activation of an autocrine loop modulating MMP expression.
Anelli
Tonino
T
Dipartimento di Biologia Cellulare e dello Sviluppo, Università La Sapienza, Piazzale A. Moro 5, 00185 Roma, Italy.
Mannello
Ferdinando
F
Salani
Monica
M
Tonti
Gaetana A
GA
Poiana
Giancarlo
G
Biagioni
Stefano
S
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology; D045744:Cell Line, Tumor; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008970:Molecular Weight; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D018678:Cholinergic Agents; D001285:Atropine; D002217:Carbachol; D002795:Choline O-Acetyltransferase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000109:Acetylcholine