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)

An improved device for potentiometry using magnetic circular dichroism spectroscopy has been developed and used to characterize the potentiometric behavior of solubilized beef heart cytochrome oxidase. In the absence of inhibitors, the electron affinity of cytochromes alpha and alpha 3 are indistinguishable and adequately described by the allosteric model of Nicholls and Peterson (Nicholls, P., and Peterson, L. C. (1972) Biochim. Biophys. Acta 357, 462-467). All of the cytochrome alpha can be accounted for as low spin heme throughout the titration. Cytochrome c present at 1:1, 2:1, and 4:1 stoichiometry with cytochrome alpha did not significantly affect the potentiometric behavior of alpha or chondroitinase alpha 3; at the 1:1 ratio the midpoint potential of cytochrome c was lowered by about 30 mV. In the presence of formate, azide and cyanide cytochrome alpha assumed approximately n = 1 behavior. However, the response of alpha 3 differed with each reagent and was particularly complex in the presence of azide. Fluoride produced very small changes in the potentiometric behavior suggesting that it may not be a ligand to cytochrome alpha 3. Possible deficiencies in the allosteric model are examined.
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PMID:Further characterization of the potentiometric behavior of cytochrome oxidase. Cytochrome alpha stays low spin during oxidation and reduction. 631 78

Using an in vitro rat incisor odontoblast system, the effect of fluoride on proteoglycans was investigated at both the metabolic and structural level. Incisors were removed from 4-week-old rats, split longitudinally, and the pulps removed. Teeth were incubated at 37 degrees C, 5% CO2 in Eagle's Minimum Essential Medium containing 35S-sulfate for 7 hours in the presence of 0 mM, 3 mM, or 6 mM sodium fluoride. Teeth were demineralized in EDTA, proteoglycan was extracted from the residue with 4 M guanidinium chloride, and further purified by anion exchange chromatography. Uptake of radiolabel was monitored by liquid scintillation counting. The resultant products were examined by cellulose acetate electrophoresis, SDS-PAGE, chondroitinase digestion, and amino acid analysis. Differential effects of fluoride were observed in both metabolism and biochemical characterization of proteoglycans following incubation at the two concentrations. Fluoride decreased uptake of the radiolabel but led to an accumulation of glycosaminoglycan within the proteoglycan of the matrix. Chondroitin sulfate was the predominant glycosaminoglycan identified, with the additional presence of dermatan sulfate and heparan sulfate identified. Dermatan sulfate levels increased in 3 mM-treated teeth. Fluoride-treated proteoglycans had a reduced molecular weight (200-90K to 180-79K); this reduction is primarily a result of smaller glycosaminoglycan chains, with limited reduction in the size of the core protein of 6 mM-treated teeth occurring. Such alterations in the biochemical metabolism and hence structure and function of proteoglycan may be implicated in the hypomineralization seen in fluorosis.
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PMID:The influence of fluoride on proteoglycan structure using a rat odontoblast in vitro system. 850 77

We examined whether enzymatic digestion of chondroitin sulfate (CS) promoted the axonal regeneration of neurons in Clarke's nucleus (CN) into a peripheral nerve (PN) graft following injury of the spinal cord. After hemisection at T11, a segment of PN graft was implanted at the lesion site. Either vehicle, brain-derived neurotrophic factor (BDNF) or chondroitinase ABC was applied at the implantation site. The postoperative survival period was 4 weeks. Treatment with vehicle or BDNF did not promote the axonal regeneration of CN neurons into the PN graft. Application of 2.5 unit/ml chondroitinase ABC resulted in a significant increase (12.8%) in the number of regenerated CN neurons. Double labeling with Fluoro-Gold and NADPH-diaphorase histochemistry showed that the regenerated CN neurons did not express nitric oxide synthase (NOS). Our results suggest that CS is inhibitory to the regeneration of CN neurons following injury of the spinal cord.
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PMID:Chondroitinase ABC promotes axonal regeneration of Clarke's neurons after spinal cord injury. 1079 Aug 83

We have previously demonstrated that enzymatic digestion of chondroitin sulfate proteoglycan (CSPG) at the scar promotes the axonal regrowth of Clarke's nucleus (CN) neurons into an implanted peripheral nerve graft after hemisection of the spinal cord. The present study examined whether degradation of CSPG using chondroitinase ABC promoted the regeneration of CN neurons through the scar into the rostral spinal cord in neonatal and adult rats. Following hemisection of the spinal cord at T11, either vehicle or chondroitinase ABC was applied onto the lesion site. The postoperative survival periods were 2 and 4 weeks. The regenerated CN neurons were retrogradely labeled by Fluoro-Gold injected at spinal cord level C7. In the sham group, there was no regeneration of injured CN neurons in both neonatal and adult rats. Treatment with 2.5 unit/ml chondroitinase ABC in neonates resulted in 11.8 and 8.3% of the injured CN neurons regenerated into the rostral spinal cord at 2 and 4 weeks, respectively. In adults, 9.4 and 12.3%, at 2 and 4 weeks, respectively, of the injured CN neurons regenerated their axons to the rostral spinal cord. The immunoreactivity for the carbohydrate epitope of CSPG was dramatically decreased around the lesion site after treatment with chondroitinase ABC compared to sham control in both neonatal and adult animals. Our results show that axonal regeneration in the spinal cord can be promoted by degradation of CSPG with chondroitinase ABC. This result further suggests that CSPG is inhibitory to the regeneration of neurons in the spinal cord after traumatic injury.
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PMID:Axonal regeneration of Clarke's neurons beyond the spinal cord injury scar after treatment with chondroitinase ABC. 1282 86

After spinal cord injury, enzymatic digestion of chondroitin sulfate proteoglycans promotes axonal regeneration of central nervous system neurons across the lesion scar. We examined whether chondroitinase ABC (ChABC) promotes the axonal regeneration of rubrospinal tract (RST) neurons following injury to the spinal cord. The effect of a GSK-3beta inhibitor, lithium chloride (LiCl), on the regeneration of axotomized RST neurons was also assessed. Adult rats received a unilateral hemisection at the seventh cervical spinal cord segment (C7). Four weeks after different treatments, regeneration of RST axons across the lesion scar was examined by injection of Fluoro-Gold at spinal segment T2, and locomotor recovery was studied by a test of forelimb usage. Injured RST axons did not regenerate spontaneously after spinal cord injury, and intraperitoneal injection of LiCl alone did not promote the regeneration of RST axons. Administration of ChABC at the lesion site enhanced the regeneration of RST axons by 20%. Combined treatment of LiCl together with ChABC significantly increased the regeneration of RST axons to 42%. Animals receiving combined treatment used both forelimbs together more often than animals that received sham or single treatment. Immunoblotting and immunohistochemical analysis revealed that LiCl induced the expression of inactive GSK-3beta as well as the upregulation of Bcl-2 in injured RST neurons. These results indicate that in vivo, LiCl inhibits GSK-3beta and reinforces the regeneration-promoting function of ChABC through a Bcl-2-dependent mechanism. Combined use of LiCl together with ChABC could be a novel treatment for spinal cord injury.
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PMID:Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. 1530 5

A number of studies have shown that chondroitinase ABC (Ch'ase ABC) digestion of inhibitory chondroitin sulfate glycosaminoglycans significantly enhances axonal growth and recovery in rodents following spinal cord injury (SCI). Further, our group has shown improved recovery following SCI in the larger cat model. The purpose of the current study was to determine whether intraspinal delivery of Ch'ase ABC, following T10 hemisections in adult cats, enhances adaptive movement features during a skilled locomotor task and/or promotes plasticity of spinal and supraspinal circuitry. Here, we show that Ch'ase ABC enhanced crossing of a peg walkway post-SCI and significantly improved ipsilateral hindlimb trajectories and integration into a functional forelimb-hindlimb coordination pattern. Recovery of these complex movements was associated with significant increases in neurofilament immunoreactivity immediately below the SCI in the ipsilateral white (p = 0.033) and contralateral gray matter (p = 0.003). Further, the rubrospinal tract is critical in the normal cat during skilled movements that require accurate paw placements and trajectories like those seen during peg walkway crossing. Rubrospinal connections were assessed following Fluoro-Gold injections, caudal to the hemisection. Significantly more retrogradely labeled right (axotomized) red nucleus (RN) neurons were seen in Ch'ase ABC-treated (23%) compared with control-treated cats (8%; p = 0.032) indicating that a larger number of RN neurons in Ch'ase ABC-treated cats had axons below the lesion level. Thus, following SCI, Ch'ase ABC may facilitate axonal growth at the spinal level, enhance adaptive features of locomotion, and affect plasticity of rubrospinal circuitry known to support adaptive behaviors in the normal cat.
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PMID:Chondroitinase ABC promotes recovery of adaptive limb movements and enhances axonal growth caudal to a spinal hemisection. 2149 Feb 12

Chondroitin sulfate proteoglycans (CSPGs) are glial scar-associated molecules considered axonal regeneration inhibitors and can be digested by chondroitinase ABC (ChABC) to promote axonal regeneration after spinal cord injury (SCI). We previously demonstrated that intrathecal delivery of low-dose ChABC (1 U) in the acute stage of SCI promoted axonal regrowth and functional recovery. In this study, high-dose ChABC (50 U) introduced via intrathecal delivery induced subarachnoid hemorrhage and death within 48 h. However, most SCI patients are treated in the sub-acute or chronic stages, when the dense glial scar has formed and is minimally digested by intrathecal delivery of ChABC at the injury site. The present study investigated whether intraparenchymal delivery of ChABC in the sub-acute stage of complete spinal cord transection would promote axonal outgrowth and improve functional recovery. We observed no functional recovery following the low-dose ChABC (1 U or 5 U) treatments. Furthermore, animals treated with high-dose ChABC (50 U or 100 U) showed decreased CSPGs levels. The extent and area of the lesion were also dramatically decreased after ChABC treatment. The outgrowth of the regenerating axons was significantly increased, and some partially crossed the lesion site in the ChABC-treated groups. In addition, retrograde Fluoro-Gold (FG) labeling showed that the outgrowing axons could cross the lesion site and reach several brain stem nuclei involved in sensory and motor functions. The Basso, Beattie and Bresnahan (BBB) open field locomotor scores revealed that the ChABC treatment significantly improved functional recovery compared to the control group at eight weeks after treatment. Our study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Thus, our results will aid in the treatment of spinal cord injury.
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PMID:Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection. 2639 21