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Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans
Cindy van der Meer-van Kraaij1, Roland Siezen, Evelien Kramer
1TI Food and Nutrition, RIKILT-Institute of Food Safety, Bornsesteeg 45, P.O box 230, 6700 AE, Wageningen, The Netherlands.
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.
Insights
Mucosal pentraxin (Mptx) in rats is regulated by diet and may indicate gut health. However, Mptx is not functional in humans due to a genetic mutation.
Area of Science:
- Biochemistry and Molecular Biology
- Gastroenterology
- Nutritional Science
Background:
- Mucosal pentraxin (Mptx) is a short pentraxin found in rats with an undetermined function.
- Mptx is predominantly expressed in the colon and is significantly regulated by dietary heme and calcium.
- Dietary heme and calcium are known modulators of colon cancer risk, suggesting Mptx's potential as a biomarker.
Purpose of the Study:
- To investigate the conserved protein structure of Mptx.
- To determine if Mptx protein expression is sensitive to dietary nutrients.
- To examine the expression of Mptx in mouse and human colons.
Main Methods:
- Sequence comparison and 3D modeling were used to assess protein structure conservation.
- Dietary heme intake was manipulated to evaluate Mptx protein expression changes.
- mRNA expression analysis was performed on rat, mouse, and human colon tissues.
Main Results:
- Rat Mptx shows high homology to other pentraxins, with conserved calcium-binding and subunit interaction sites.
- Mptx protein levels in rat colon mucosa were significantly downregulated with high dietary heme intake.
- Mptx mRNA is expressed in rat and mouse colon but absent in human colon due to a premature stop codon.
Conclusions:
- Mptx is a nutrient-sensitive protein in the rat colon, potentially serving as a biomarker for gut health.
- The structural and functional conservation of Mptx varies across species.
- A loss-of-function mutation in humans suggests differences in intestinal cell turnover compared to rodents.
