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Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans

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Abstract

Mucosal pentraxin (Mptx), identified in rats, is a short pentraxin of unknown function. Other subfamily members are Serum amyloid P component (SAP), C-reactive protein (CRP) and Jeltraxin. Rat Mptx mRNA is predominantly expressed in colon and in vivo is strongly (30-fold) regulated by dietary heme and calcium, modulators of colon cancer risk. This renders Mptx a potential nutrient sensitive biomarker of gut health. To support a role as biomarker, we examined whether the pentraxin protein structure is conserved, whether Mptx protein is nutrient-sensitively expressed and whether Mptx is expressed in mouse and human. Sequence comparison and 3D modelling showed that rat Mptx is highly homologous to the other pentraxins. The calcium-binding site and subunit interaction sites are highly conserved, while a loop deletion and charged residues contribute to a distinctive “top” face of the pentamer. In accordance with mRNA expression, Mptx protein is strongly down-regulated in rat colon mucosa in response to high dietary heme intake. Mptx mRNA is expressed in rat and mouse colon, but not in human colon. A stop codon at the beginning of human exon two indicates loss of function, which may be related to differences in intestinal cell turnover between man and rodents.

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Acknowledgments

We thank D. Jonker-Termont (NIZO food research, Ede, The Netherlands) and B. Weijers (Small Animal Research Centre, Wageningen, The Netherlands) for expert technical assistance, Prof. Dr. J. Kleibeuker (University Groningen, The Netherlands) for assistance in provision of human colon biopsy cDNA, Prof. Dr. M. Katan (WCFS) for helpful discussions and Dr. B. Renckens and Dr. C. van Gelder (CMBI) for assistance with homology modelling and for useful discussions.

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Authors and Affiliations

  1. TI Food and Nutrition, RIKILT-Institute of Food Safety, Bornsesteeg 45, P.O box 230, 6700 AE, Wageningen, The Netherlands

    Cindy van der Meer-van Kraaij, Roland Siezen, Evelien Kramer, Marjolein Reinders, Roelof van der Meer & Jaap Keijer

  2. RIKILT, Institute of Food Safety, Wageningen, The Netherlands

    Cindy van der Meer-van Kraaij, Evelien Kramer, Marjolein Reinders & Jaap Keijer

  3. NIZO food research, Ede, The Netherlands

    Cindy van der Meer-van Kraaij, Roland Siezen & Roelof van der Meer

  4. Center for Molecular and Biomolecular Informatics (CMBI), Nijmegen, The Netherlands

    Roland Siezen

  5. Rijksuniversiteit Groningen, Groningen, The Netherlands

    Hans Blokzijl

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  1. Cindy van der Meer-van Kraaij
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Correspondence to Jaap Keijer.

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van der Meer-van Kraaij, C., Siezen, R., Kramer, E. et al. Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans. Genes Nutr 2, 275–285 (2007). https://doi.org/10.1007/s12263-007-0058-x

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  • DOI: https://doi.org/10.1007/s12263-007-0058-x

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