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Perally, S., LaCourse, James 
ORCID: https://orcid.org/0000-0001-9261-7136, Campbell, A. M. and Brophy, P. M.
(2008)
'Heme transport and detoxification in nematodes: Subproteomics evidence of differential role of glutathione transferases'. Journal of Proteome Research, Vol 7, Issue 10, pp. 4557-4565.
Abstract
In contrast to their mammalian hosts, parasitic nematodes are heme auxotrophs and require pathways for the uptake and transport of exogenous heme for incorporation into hemoproteins. Phase II detoxification Nu-class glutathione transferase (GST) proteins have a proposed role as heme-binding ligandins in parasitic nematodes. The genome-verified free-living nematode Caenorhabditis elegans also cannot synthesize heme and is an ideal functional genomics model to delineate the role of individual nematode GSTs in heme trafficking and heme detoxification. In this study, C, elegans was exposed to externally controlled heme concentrations ranging from 20-fold suboptimal growth levels to 10-fold supra-optimal growth levels to mimic fluctuations in blood- and tissue-feeding parasitic cousins from the same nematode group. A new heme-responsive GST (GST-19) was identified by subproteomics approaches. Functional characterization of this and two other C. elegans GSTs revealed that they all have high affinity for heme compounds similar to mammalian soluble heme carrier proteins such as HBP23 (K-d approximate to 10(-8) M). In the genomics-predicted absence of orthologous mammalian soluble heme-binding proteins in nematodes, we propose that Nu-class GSTs are candidates in the cellular processing of heme compounds. Toxic heme binding may be coupled to enzymatic protection from its breakdown as several GSTs possess glutathione peroxidase activity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | glutathione transferase heme transport detoxification caenorhabditis elegans nematode hookworm necator-americanus caenorhabditis-elegans s-transferases parasitic nematode c-elegans heligmosomoides-polygyrus functional-analysis life-span identification resistance |
| Subjects: | QX Parasitology > Helminths. Annelida > QX 203 Nematoda |
| Faculty: Department: | Groups (2002 - 2012) > Disease Control Strategy Group |
| Digital Object Identifer (DOI): | https://doi.org/10.1021/pr800395x |
| Depositing User: | Ms Julia Martin |
| Date Deposited: | 26 Jul 2010 15:33 |
| Last Modified: | 06 Feb 2018 13:00 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/892 |
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