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Conference Paper: The Mechanisms of Chondroitin Sulphate Lyases Treatment in Promotion of Axonal Growth
Title | The Mechanisms of Chondroitin Sulphate Lyases Treatment in Promotion of Axonal Growth |
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Authors | |
Issue Date | 2012 |
Citation | The 2012 Hong Kong-Taiwan Physiology Symposium and Joint Scientific Meeting of Hong Kong Society of Neurosciences (HKSN) and The Biophysical Society of Hong Kong (BSHK), The Chinese University of Hong Kong, Hong Kong, China, 14-15 June 2012, p. 72-73, abstract no. P57 How to Cite? |
Abstract | In Injured nerves, chondroitin sulphate (CS) is upregulated forming barriers with astrocytes/fibroblasts and
other extracellular matrix molecules, and thereby hampering nerve regeneration. Cleavage of CS using
chondroitin sulphate lyases (Proteus vulgaris) promises axon regrowth through the barrier but the
enzymatic efficacy remains to be improved. Two subtypes, endolyase and exolyase, have been found
coexisting in the original host but only the former has been exploited for treatment of injured nerve tracts. We hypothesise that the two subtypes are necessary for enzymatic efficacy on CSs. We therefore
prepared recombinant enzymes of both subtypes. Enzyme kinetics study revealed feedback inhibition by
limit digestion products: that of the endolyase by tetrasaccharides and that of the exolyase by the
disaccharides. When the two subtypes were used in combination, the digestion efficiency increased.
We then used TGF beta-1 to induce CS production by astrocytes in culture, mimicking reactive glia in
injured nerves. In co-cultures of such astrocytes with cortical neurons, treatment with combinations of
the two subtypes resulted in increased neurite lengths as compared to co-cultures treated with one of the
subtypes. The limit digestion products of CS were further tested for their effects on neurite extension on
astrocytes that had been treated with TGF beta-1. The CS disaccharides, both 4- and 6-sulphated but not
the tetrasaccharides, promoted neurite extension significantly. Taken together, the combinatorial use of
the ChABC subtypes not only improved efficacy of enzyme activity on the axon-restrictive CS moiety, but
also increased the yield of CS disaccharides which contributed to axonal growth. |
Description | Poster Presentation |
Persistent Identifier | http://hdl.handle.net/10722/153015 |
DC Field | Value | Language |
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dc.contributor.author | Tam, KW | en_US |
dc.contributor.author | Chan, YS | en_US |
dc.contributor.author | Shum, DKY | en_US |
dc.date.accessioned | 2012-07-16T09:54:55Z | - |
dc.date.available | 2012-07-16T09:54:55Z | - |
dc.date.issued | 2012 | en_US |
dc.identifier.citation | The 2012 Hong Kong-Taiwan Physiology Symposium and Joint Scientific Meeting of Hong Kong Society of Neurosciences (HKSN) and The Biophysical Society of Hong Kong (BSHK), The Chinese University of Hong Kong, Hong Kong, China, 14-15 June 2012, p. 72-73, abstract no. P57 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/153015 | - |
dc.description | Poster Presentation | - |
dc.description.abstract | In Injured nerves, chondroitin sulphate (CS) is upregulated forming barriers with astrocytes/fibroblasts and other extracellular matrix molecules, and thereby hampering nerve regeneration. Cleavage of CS using chondroitin sulphate lyases (Proteus vulgaris) promises axon regrowth through the barrier but the enzymatic efficacy remains to be improved. Two subtypes, endolyase and exolyase, have been found coexisting in the original host but only the former has been exploited for treatment of injured nerve tracts. We hypothesise that the two subtypes are necessary for enzymatic efficacy on CSs. We therefore prepared recombinant enzymes of both subtypes. Enzyme kinetics study revealed feedback inhibition by limit digestion products: that of the endolyase by tetrasaccharides and that of the exolyase by the disaccharides. When the two subtypes were used in combination, the digestion efficiency increased. We then used TGF beta-1 to induce CS production by astrocytes in culture, mimicking reactive glia in injured nerves. In co-cultures of such astrocytes with cortical neurons, treatment with combinations of the two subtypes resulted in increased neurite lengths as compared to co-cultures treated with one of the subtypes. The limit digestion products of CS were further tested for their effects on neurite extension on astrocytes that had been treated with TGF beta-1. The CS disaccharides, both 4- and 6-sulphated but not the tetrasaccharides, promoted neurite extension significantly. Taken together, the combinatorial use of the ChABC subtypes not only improved efficacy of enzyme activity on the axon-restrictive CS moiety, but also increased the yield of CS disaccharides which contributed to axonal growth. | - |
dc.language | eng | en_US |
dc.relation.ispartof | Hong Kong-Taiwan Physiology Symposium & HKSN-BSHK 2012 Joint Scientific Meeting | en_US |
dc.title | The Mechanisms of Chondroitin Sulphate Lyases Treatment in Promotion of Axonal Growth | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Tam, KW: antam@graduate.hku.hk | en_US |
dc.identifier.email | Chan, YS: yschan@hku.hk | en_US |
dc.identifier.email | Shum, DKY: shumdkhk@hkucc.hku.hk | en_US |
dc.identifier.authority | Chan, YS=rp00318 | en_US |
dc.identifier.authority | Shum, DKY=rp00321 | en_US |
dc.description.nature | published_or_final_version | - |
dc.identifier.hkuros | 200594 | en_US |
dc.identifier.spage | 72, abstract no. P57 | - |
dc.identifier.epage | 73, abstract no. P57 | - |