Dissociation of neurite-promoting activity and protease-inhibiting function of alpha 2-macroglobulin in culture.
The relationship between the neurite-promoting effect and the protease-inhibiting function of alpha 2-macroglobulin (alpha 2M) was examined in a culture of dissociated neurons from embryonic rat neocortical tissue. The neurite-promoting effect of various protease inhibitors (soybean trypsin inhibitor, alpha 1-antitrypsin, aprotinin, phenylmethanesulfonyl fluoride, leupeptin, antipain, human alpha 2M and purified rat alpha 2M) was investigated. At lower concentrations, only alpha 2M significantly promoted neurite outgrowth. Furthermore, alpha 2M-trypsin complexes, which had lost their protease-inhibiting function and exposed their receptor-recognition site, promoted neurite outgrowth more efficiently than native alpha 2M. These results indicate the possibility that the neurite-promoting effect of alpha 2M is mediated by its receptor-binding activity but is not directly related to its protease-inhibiting function.
Mori
T
T
Biochemical Research Section, Asahi Breweries, Ltd., Tokyo, Japan.
Miyamoto
Y
Y
Iijima
N
N
Kitabatake
K
K
Kohsaka
S
S
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D016501:Neurites / Q000187:drug effects*; D015849:Plasminogen Inactivators / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D058255:Protease Nexins; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface; D013268:Stimulation, Chemical; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D015849:Plasminogen Inactivators; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D000511:alpha-Macroglobulins