Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans.
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.
van der Meer-van Kraaij
Cindy
C
TI Food and Nutrition, RIKILT-Institute of Food Safety, Bornsesteeg 45, P.O box 230, 6700 AE, Wageningen, The Netherlands.
Siezen
Roland
R
Kramer
Evelien
E
Reinders
Marjolein
M
Blokzijl
Hans
H
van der Meer
Roelof
R
Keijer
Jaap
J