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Journal of Neuroscience, Vol 11, 822-827, Copyright © 1991 by Society for Neuroscience
Inhibitory effects of brain chondroitin sulfate proteoglycans on neurite outgrowth from PC12D cells
A Oohira, F Matsui and R Katoh-Semba
Department of Embryology, Institute for Developmental Research, Aichi, Japan.
Soluble chondroitin sulfate proteoglycans (CSPGs), prepared from 10-d- old
rat brain, were added to the culture medium of PC12D cells containing NGF
to examine the effects on NGF-induced neurite outgrowth from the cells.
PC12D cells, a flat-shaped variant of PC12 pheochromocytoma cells, are
characteristic of prompt neurite formation in response not only to NGF, but
also to cAMP-enhancing reagents such as forskolin. Brain CSPGs inhibited
the neurite elongation irreversibly in a dose-dependent manner; complete
inhibition was observed at a concentration of 50 nmol uronic acid/ml.
Closely similar dose-dependent inhibition was observed in the
forskolin-induced neurite outgrowth from PC12D cells. NGF-induced neurite
outgrowth from conventional PC12 cells was also inhibited completely by 50
nmol uronic acid/ml CSPGs. Some brain CSPGs seemed to be inhibitory, but
the cartilage-unique CSPG did not show any inhibitory effect. Chondroitin
sulfate, a polysaccharide moiety of CSPGs, did not show any inhibitory
effect even at a concentration of 250 nmol uronic acid/ml, while core
proteins prepared from brain CSPGs by digestion with chondroitinase ABC
exhibited inhibitory activity similar to that of intact CSPGs. This
indicates that the site of the inhibitory activity exists in the core
protein moiety of brain CSPGs. From these observations, it is conceivable
that brain CSPGs are involved in the regulation of neuronal
differentiation.
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