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

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

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    9 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)275-285
    Number of pages11
    JournalGenes and nutrition
    Volume2
    Issue number3
    DOIs
    Publication statusPublished - Dec-2007

    Keywords

    • heme
    • calcium
    • carcinogenesis
    • nutrition
    • biomarker
    • protein modelling
    • absence in human
    • C-REACTIVE PROTEIN
    • AMYLOID-P COMPONENT
    • GAMMA-LACTONE OXIDASE
    • COLON-CANCER
    • RED MEAT
    • APOPTOTIC CELLS
    • GENE-EXPRESSION
    • ASCORBIC-ACID
    • HEME
    • SEQUENCE

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