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 sulphate/dermatan sulphate proteoglycan (CDSPG) that co-eluted with a heparan sulphate proteoglycan (HSPG) by ion-exchange chromatography. The CDSPG 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 digestion and urea/polyacrylamide gel electrophoresis established the homogeneity of the CDSPG and suggested molecular masses of the core protein and glycosylated protein as 54 kDa and 58 kDa respectively. Virtually all of the poly-D-lysine substrate-bound proteoglycan-associated neurite growth-promoting activity of astrocyte CM was accounted for by the HSPG. On poly-D-lysine the immobilized CDSPG displayed little neurite growth-stimulatory activity relative to the HSPG. However, the CDSPG inhibited the potent growth-promoting activity of the HSPG by displacing it from the poly-D-lysine substrate. Differential cellular regulation of production of growth-modulatory proteins with different binding avidity for the substrate of growth may determine the success of a regenerative axonal response by fully competent neurons.