ArticleThe Journal of biological chemistry2014
The MF6p/FhHDM-1 major antigen secreted by the trematode parasite Fasciola hepatica is a heme-binding protein.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Hooked on fish blood: the reliance of a gill parasite on haematophagy.Proceedings. Biological sciences · 2024Article
- Increased specificity of Fasciola hepatica excretory-secretory antigens combining negative selection on hydroxyapatite and salt precipitation.Scientific reports · 2024Article
- Exploring extracellular vesicles in zoonotic helminth biology: implications for diagnosis, therapeutic and delivery.Frontiers in cellular and infection microbiology · 2024Review
- An Update on the Pathogenesis of Fascioliasis: What Do We Know?Research and reports in tropical medicine · 2024Review
- Transcriptome Profile Analyses of Head Kidney in Roach (Biology · 2023Article
- Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles.PLoS neglected tropical diseases · 2022Article
- Pathogenicity and virulence of the liver flukesVirulence · 2021Article
- Complementary transcriptomic and proteomic analyses reveal the cellular and molecular processes that drive growth and development of Fasciola hepatica in the host liver.BMC genomics · 2021Article
- Schistosoma mansoni immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs).PLoS neglected tropical diseases · 2020Article
- Clonorchis sinensis MF6p/HDM (CsMF6p/HDM) induces pro-inflammatory immune response in RAW 264.7 macrophage cells via NF-κB-dependent MAPK pathways.Parasites & vectors · 2020Article
- Article
- Comparison of recombinant cathepsins L1, L2, and L5 as ELISA targets for serodiagnosis of bovine and ovine fascioliasis.Parasitology research · 2018Article
- Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms.International journal of molecular sciences · 2017Review
- Delineating distinct heme-scavenging and -binding functions of domains in MF6p/helminth defense molecule (HDM) proteins from parasitic flatworms.The Journal of biological chemistry · 2017Article
- Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins.PloS one · 2017Article
- Conservation and diversification of the transcriptomes of adult Paragonimus westermani and P. skrjabini.Parasites & vectors · 2016Article
- Across intra-mammalian stages of the liver f luke Fasciola hepatica: a proteomic study.Scientific reports · 2016Article
- Rapid Enhanced MM3-COPRO ELISA for Detection of Fasciola Coproantigens.PLoS neglected tropical diseases · 2016Article
- Usefulness of ELISA Methods for Assessing LPS Interactions with Proteins and Peptides.PloS one · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood-feeding parasites have developed biochemical mechanisms to control heme intake and detoxification. Here we show that a major antigen secreted by Fasciola hepatica, previously reported as MF6p, of unknown function (gb|CCA61804.1), and as FhHDM-1, considered to be a helminth defense molecule belonging to the family of cathelicidin-like proteins (gb|ADZ24001.1), is in fact a heme-binding protein. The heme-binding nature of the MF6p/FhHDM-1 protein was revealed in two independent experiments: (i) immunopurification of the secreted protein·heme complexes with mAb MF6 and subsequent analysis by C8 reversed-phase HPLC and MS/MS spectrometry and (ii) analysis of the binding ability of the synthetic protein to hemin in vitro. By immunohistochemistry analysis, we have observed that MF6p/FhHDM-1 is produced by parenchymal cells and transported to other tissues (e.g. vitellaria and testis). Interestingly, MF6p/FhHDM-1 is absent both in the intestinal cells and in the lumen of cecum, but it can be released through the tegumental surface to the external medium, where it binds to free heme molecules regurgitated by the parasite after hemoglobin digestion. Proteins that are close analogs of the Fasciola MF6p/FhHDM-1 are present in other trematodes, including Clonorchis, Opistorchis, Paragonimus, Schistosoma, and Dicrocoelium. Using UV-visible spectroscopy and immunoprecipitation techniques, we observed that synthetic MF6p/FhHDM-1 binds to hemin with 1:1 stoichiometry and an apparent Kd of 1.14 × 10(-6) M(-1). We also demonstrated that formation of synthetic MF6p/FhHDM-1·hemin complexes inhibited hemin degradation by hydrogen peroxide and hemin peroxidase-like activity in vitro. Our results suggest that MF6p/FhHDM-1 may be involved in heme homeostasis in trematodes.
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