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.
TI Food and Nutrition, RIKILT-Institute of Food Safety, Bornsesteeg 45, P.O box 230, 6700 AE, Wageningen, The Netherlands.
Cindy
C
van der Meer-van Kraaij
Roland
R
Siezen
Evelien
E
Kramer
Marjolein
M
Reinders
Hans
H
Blokzijl
Roelof
R
van der Meer
Jaap
J
Keijer