Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PTP zeta is a receptor-type protein-tyrosine phosphatase that is synthesized as a chondroitin sulfate proteoglycan and uses pleiotrophin as a ligand. The chondroitin sulfate portion of this receptor is essential for high affinity binding to pleiotrophin. Here, we purified phosphacan, which corresponds to the extracellular domain of PTP zeta, from postnatal day 7 (P7) and P12 rat cerebral cortex (PG-P7 and PG-P12, respectively) and from P20 rat whole brain (PG-P20). The chondroitin sulfate of these preparations displayed immunologically and compositionally different structures. In particular, only PG-P20 reacted with the monoclonal antibody MO-225, which recognizes chondroitin sulfate containing the GlcA(2S)beta 1-3GalNAc(6S) disaccharide unit (D unit). Analysis of the chondroitinase digestion products revealed that GlcA beta 1-3GalNAc(4S) disaccharide unit (A unit) was the major component in these preparations and that PG-P20 contained 1.3% D unit, which was not detected in PG-P7 and PG-P12. Interaction analysis using a surface plasmon resonance biosensor indicated that PG-P20 had approximately 5-fold stronger affinity for pleiotrophin (dissociation constant (KD) = 0.14 nM) than PG-P7 and PG-P12, although all these preparations showed similar low affinity binding to pleiotrophin after chondroitinase ABC digestion (KD = 1.4 approximately 1.6 nM). We also found that shark cartilage chondroitin sulfate D containing approximately 20% D unit bound to pleiotrophin with moderate affinity (KD = 2.7 nM), whereas whale cartilage chondroitin sulfate A showed no binding to this growth factor. These results suggest that variation of chondroitin sulfate plays important roles in the regulation of signal transduction in the brain.
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PMID:Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 proteoglycan regulates its binding affinity for pleiotrophin/heparin binding growth-associated molecule. 1284 14

Severed axons of the inferior colliculus (IC) commissure can regenerate across a lesion in organotypic cultures from postnatal day (P) 6 gerbils, but this regenerative capacity is lost by P12 (Hafidi et al. [ 1995] J Neurosci 15:1298-1307, [1999] J Neurobiol 41:267-280). In the present study, we examined the mechanisms underlying this age-dependent failure of axons to regenerate. In P6-P12 heterochronic cultures, the P12 axons failed to cross the lesion site and project to the contralateral P6 IC lobe. In contrast, axons originating from the P6 lobe could regenerate through the lesion and invade the contralateral P12 IC lobe. To determine whether this age-dependent change in regenerative capacity can develop in organotypic cultures, IC slices with an intact commissure were obtained from P6 animals, grown in vitro for 6 days, and then lesioned at the commissure. In these slices, axon regeneration failure was similar to that observed in normal P12 tissue. Several in vitro treatments enhanced axon regeneration: removal of the entire midline region, inhibition of protein synthesis at the lesion site, and exposure to ABC chondroitinase. Furthermore, when the injured commissural axons were provided with a carpet of C6-R cells (a radial glia-like cell line), significantly more axons projected to the contralateral lobe of the IC. Taken together, these results suggest that the maturation of nonneuronal cells within the lesion site lead to failed axon regeneration in mature animals, and show that ameliorative strategies can be evaluated in vitro.
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PMID:In vitro analysis of mechanisms underlying age-dependent failure of axon regeneration. 1475 27