NOVEL NEURITE GROWTH-INHIBITORY PROPERTIES OF AN ASTROCYTE PROTEOGLYCAN

Conditioned medium (CM) of primary cultures of GFAP-positive adherent astrocytes from neonatal rat neocortex contained a chondroitin sulphat e/dermatan sulphate proteoglycan (CDSPG) that co-eluted with a heparan sulphate proteoglycan (HSPG) by ion-exchange chromatography. The CDSP G was resolved from the HSPG by molecular sieve chromatography, which indicated that the molecular mass of the HSPG was greater than 300 kDa , while that of the CDSPG was approximately 50 kDa. Specific lyase dig estion and urea/polyacrylamide gel electrophoresis established the hom ogeneity of the CDSPG and suggested molecular masses of the core prote in and glycosylated protein as 54 kDa and 58 kDa respectively. Virtual ly all of the poly-D-lysine substrate-bound proteoglycan-associated ne urite growth-promoting activity of astrocyte CM was accounted for by t he HSPG. On poly-D-lysine the immobilized CDSPG displayed little neuri te growth-stimulatory activity relative to the HSPG. However, the CDSP G inhibited the potent growth-promoting activity of the HSPG by displa cing it from the poly-D-lysine substrate. Differential cellular regula tion of production of growth-modulatory proteins with different bindin g avidity for the substrate of growth may determine the success of a r egenerative axonal response by fully competent neurons.