Thioredoxins of a parasitic nematode: Comparison of the 16- and 12-kDA thioredoxins from Haemonchus contortus

Sotirchos, IM; Hudson, AL; Ellis, J; Davey, MW

Thioredoxins of a parasitic nematode: Comparison of the 16- and 12-kDA thioredoxins from Haemonchus contortus

Sotirchos, IM Hudson, AL Ellis, J

Davey, MW

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Publication Type:: Journal Article
Citation:: Free Radical Biology and Medicine, 2008, 44 (12), pp. 2026 - 2033
Issue Date:: 2008-06-15

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Field	Value	Language
dc.contributor.author	Sotirchos, IM	en_US
dc.contributor.author	Hudson, AL	en_US
dc.contributor.author	Ellis, J https://orcid.org/0000-0001-7328-4831	en_US
dc.contributor.author	Davey, MW	en_US
dc.date.available	2008-03-10	en_US
dc.date.issued	2008-06-15	en_US
dc.identifier.citation	Free Radical Biology and Medicine, 2008, 44 (12), pp. 2026 - 2033	en_US
dc.identifier.issn	0891-5849	en_US
dc.identifier.uri	http://hdl.handle.net/10453/8653
dc.description.abstract	Thioredoxins are a family of small proteins conserved through evolution, which are essential for the maintenance of cellular homeostasis. The "classic" thioredoxin, identified in most species, is a 12-kDa protein with a Cys-Pro-Gly-Cys (CPGC) active site. However, in nematodes a larger protein, 16 kDa, with a Cys-Pro-Pro-Cys (CPPC) active site was identified. We report that in the parasitic nematode Haemonchus contortus, both the 12-kDa (HcTrx1) and the 16-kDa (HcTrx3) species are expressed through the life cycle. However, the HcTrx3 is expressed at higher concentrations. Recombinant HcTrx1 and HcTrx3 were produced and both reduced insulin at a rate similar to that observed with ovine (host) and Escherichia coli thioredoxins and both were regenerated by a mammalian thioredoxin reductase, demonstrating that they have similar thioredoxin activity. Unlike mammalian thioredoxins, both proteins were able to reduce oxidised glutathione and hydrogen peroxide. This suggests essential roles for these proteins in response to oxidative stress and the host immune attack. Analysis of ivermectin-resistant H. contortus showed that expression of both genes were increased in a drug-resistant strain relative to a sensitive strain. Involvement in drug resistance identifies these thioredoxin proteins as potential drug targets for parasite control. © 2008 Elsevier Inc. All rights reserved.	en_US
dc.relation.ispartof	Free Radical Biology and Medicine	en_US
dc.relation.isbasedon	10.1016/j.freeradbiomed.2008.03.007	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Haemonchus	en_US
dc.subject.mesh	Binding Sites	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Protein Conformation	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.subject.mesh	Thioredoxins	en_US
dc.title	Thioredoxins of a parasitic nematode: Comparison of the 16- and 12-kDA thioredoxins from Haemonchus contortus	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	44	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
dc.location.activity	ISI:000256579600005	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	44	en_US

Abstract:

Thioredoxins are a family of small proteins conserved through evolution, which are essential for the maintenance of cellular homeostasis. The "classic" thioredoxin, identified in most species, is a 12-kDa protein with a Cys-Pro-Gly-Cys (CPGC) active site. However, in nematodes a larger protein, 16 kDa, with a Cys-Pro-Pro-Cys (CPPC) active site was identified. We report that in the parasitic nematode Haemonchus contortus, both the 12-kDa (HcTrx1) and the 16-kDa (HcTrx3) species are expressed through the life cycle. However, the HcTrx3 is expressed at higher concentrations. Recombinant HcTrx1 and HcTrx3 were produced and both reduced insulin at a rate similar to that observed with ovine (host) and Escherichia coli thioredoxins and both were regenerated by a mammalian thioredoxin reductase, demonstrating that they have similar thioredoxin activity. Unlike mammalian thioredoxins, both proteins were able to reduce oxidised glutathione and hydrogen peroxide. This suggests essential roles for these proteins in response to oxidative stress and the host immune attack. Analysis of ivermectin-resistant H. contortus showed that expression of both genes were increased in a drug-resistant strain relative to a sensitive strain. Involvement in drug resistance identifies these thioredoxin proteins as potential drug targets for parasite control. © 2008 Elsevier Inc. All rights reserved.

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http://hdl.handle.net/10453/8653