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Conference Paper: Overcoming the chondroitin sulphate barrier in injured nerve: the efficacy of chondroitinase ABC treatment and the potency of disaccharide products

TitleOvercoming the chondroitin sulphate barrier in injured nerve: the efficacy of chondroitinase ABC treatment and the potency of disaccharide products
Authors
Issue Date2014
PublisherResearch Centre of Heart, Brain, Hormone & Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong.
Citation
The 9th International Symposium on Healthy Aging, Hong Kong, China, 8-9 March 2014 How to Cite?
AbstractChondroitin sulphate proteoglycans (CSPGs) up-regulated in the extracellular matrix of injured nerves, constitute barriers to nerve regeneration. Cleavage of CS using chondroitinase ABC (Proteus vulgaris) promises axon regrowth through the barrier. Albeit the occurrence of two subtypes (ChABCI, an endolyase, and ChABC II, and exolyase), only ChABC I is commercially available and tested for medical use. We produced recombinant (r) forms of the two subtypes and found that rChABC I was subject to competitive inhibition by the limit digestion product, CS-tetrasaccharides. Inclusion of rChABC II in the digestion mixture yielded essentially CS-disaccharides that were not inhibitors of rChABC I. Combinatorial use of both rChABC subtypes therefore improved efficiency of the CS-cleaving reaction and resulted in increased neurite lengths in a coculture model of cortical neurons with TGFβ1-stimulated astrocytes. Neurites growth-promoting effects of CS digestion products were revealed in cocultures with had been treated with rChABC combinations, washed of digestion products and then treated with graded supplements of CS-type ΔDi-4S or ΔDi-6S. By contrast, control treatments with sucrose or CS-type tetrasaccharides did not promote neurite growth . Evidence is thus provided for the dual role of combinatorial ChABC activities, both in cleaving the putative CS barrier to axon growth, and yielding CS-type disaccharide products that contribute to neurite growth.
DescriptionConference Theme: Aging with Confidence
Persistent Identifierhttp://hdl.handle.net/10722/201177

 

DC FieldValueLanguage
dc.contributor.authorTam, KWen_US
dc.contributor.authorChan, YSen_US
dc.contributor.authorShum, DKYen_US
dc.date.accessioned2014-08-21T07:16:31Z-
dc.date.available2014-08-21T07:16:31Z-
dc.date.issued2014en_US
dc.identifier.citationThe 9th International Symposium on Healthy Aging, Hong Kong, China, 8-9 March 2014en_US
dc.identifier.urihttp://hdl.handle.net/10722/201177-
dc.descriptionConference Theme: Aging with Confidence-
dc.description.abstractChondroitin sulphate proteoglycans (CSPGs) up-regulated in the extracellular matrix of injured nerves, constitute barriers to nerve regeneration. Cleavage of CS using chondroitinase ABC (Proteus vulgaris) promises axon regrowth through the barrier. Albeit the occurrence of two subtypes (ChABCI, an endolyase, and ChABC II, and exolyase), only ChABC I is commercially available and tested for medical use. We produced recombinant (r) forms of the two subtypes and found that rChABC I was subject to competitive inhibition by the limit digestion product, CS-tetrasaccharides. Inclusion of rChABC II in the digestion mixture yielded essentially CS-disaccharides that were not inhibitors of rChABC I. Combinatorial use of both rChABC subtypes therefore improved efficiency of the CS-cleaving reaction and resulted in increased neurite lengths in a coculture model of cortical neurons with TGFβ1-stimulated astrocytes. Neurites growth-promoting effects of CS digestion products were revealed in cocultures with had been treated with rChABC combinations, washed of digestion products and then treated with graded supplements of CS-type ΔDi-4S or ΔDi-6S. By contrast, control treatments with sucrose or CS-type tetrasaccharides did not promote neurite growth . Evidence is thus provided for the dual role of combinatorial ChABC activities, both in cleaving the putative CS barrier to axon growth, and yielding CS-type disaccharide products that contribute to neurite growth.en_US
dc.languageengen_US
dc.publisherResearch Centre of Heart, Brain, Hormone & Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong.-
dc.relation.ispartofInternational Symposium on Healthy Agingen_US
dc.titleOvercoming the chondroitin sulphate barrier in injured nerve: the efficacy of chondroitinase ABC treatment and the potency of disaccharide productsen_US
dc.typeConference_Paperen_US
dc.identifier.emailTam, KW: antam@graduate.hku.hken_US
dc.identifier.emailChan, YS: yschan@hku.hken_US
dc.identifier.emailShum, DKY: shumdkhk@hkucc.hku.hken_US
dc.identifier.authorityChan, YS=rp00318en_US
dc.identifier.hkuros234874en_US
dc.publisher.placeHong Kong-

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