Neurite-promoting effect of alpha 2-macroglobulin in rat cerebral cortex is mainly associated with alpha 2-macroglobulin receptor.
It has been reported that alpha 2-macroglobulin (alpha 2 M), known as a plasma protease inhibitor, promotes neurite outgrowth of cultured neurons from rat cerebral cortex. The neurons dissociated from 17-day embryonic (E17) rat cerebral cortex were cultured in the medium containing methylamine-modified alpha 2M labeled with fluorescein isothiocyanate (MA- alpha 2 M-FITC). The modified alpha 2 M was taken up by neurons and localized mainly at the base of neurites. The fluorescence intensity of internalized MA- alpha 2 M-FITC in the cell was correlated to the degree of neurites extension. An immunocytochemical study using anti-alpha 2 M receptor (alpha 2 MR) polyclonal antibody showed that the neurons cultured for a longer period were stained weaker than those cultured for a shorter period. Many alpha 2 MRs were expressed when the neurons were likely to be extending the neurites well. From the developmental study of rat cerebrum, the expression of alpha 2 MR reached a maximum at postnatal 2 days (P2) when the neurons started to exhibit active neurite extension. These observations led us to conclude that neurite promoting effect of alpha 2 M acts through alpha 2 M-alpha 2MR binding and/or the following uptake of alpha 2 M.
Ishii
M
M
Department of Biological Sciences, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Osada
T
T
Gliemann
J
J
Ikai
A
A
D000818:Animals; D000918:Antibody Specificity; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D005333:Fetus / Q000166:cytology; D016650:Fluorescein-5-isothiocyanate; D005455:Fluorescent Antibody Technique; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D016501:Neurites / Q000737:chemistry / Q000187:drug effects*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000032:analysis* / Q000276:immunology; D000511:alpha-Macroglobulins / Q000493:pharmacokinetics / Q000494:pharmacology*
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D016650:Fluorescein-5-isothiocyanate