Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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In mammals, the matrix extracellular phosphoglycoprotein (MEPE) is known to activate osteogenesis and mineralization via a particular region called dentonin, and to inhibit mineralization via its ASARM (acidic serine-aspartate rich MEPE-associated motif) peptide that also plays a role in phosphatemia regulation. In order to understand MEPE evolution in mammals, and particularly that of its functional regions, we conducted an evolutionary analysis based on the study of selective pressures. Using 37 mammalian sequences we: (1) confirmed the presence of an additional coding exon in most placentals; (2) highlighted several conserved residues and regions that could have important functions; (3) found that dentonin function was recruited in a placental ancestor; and (4) revealed that ASARM function was present earlier, pushing the recruitment of MEPE deep into amniote origins. Our data indicate that MEPE was involved in various functions (bone and eggshell mineralization) prior to acquiring those currently known in placental mammals.
Cell Mol Life Sci 2010 Jan
PMID:MEPE evolution in mammals reveals regions and residues of prime functional importance. 1992 83

In chicken, ovocleidin 116 (OC-116) is found in the eggshell matrix and its encoding gene, OC-116, is expressed in uterine cells. In mammals, its orthologue MEPE encodes the matrix extracellular phosphoglycoprotein (MEPE), which has been shown to be involved in bone mineralization. Using RT-PCR and in situ hybridization on sections, we have checked whether OC-116 was also expressed in osteoblasts and osteocytes during bone development and mineralization in chicken embryos. We monitored OC-116 expression in the tibia and mandible of a growth series of chicken embryos from E3 to E19. Transcripts were identified in the osteoblasts as early as E5 in the tibia and E7 in the mandible, before matrix mineralization, then from these stages onwards in both the osteoblasts lining the mineralized bone matrix and the osteocytes. Therefore, early in chicken ontogeny and as soon as osteogenesis begins, OC-116 is involved. Its function, which remains still unknown, is maintained during further bone growth and mineralization, and later in adult, in which it is recruited for eggshell formation. We hypothesize that the ancestral OC-116/MEPE in a stem amniote was involved in these two functions and that the loss of eggshell in the mammalian lineage has probably favored the recruitment of some MEPE domains toward new functions in osteogenesis and mineralization, and in phosphatemia regulation.
J Exp Zool B Mol Dev Evol 2010 Dec 15
PMID:OC-116, the chicken ortholog of mammalian MEPE found in eggshell, is also expressed in bone cells. 2066 9

Milk fever (MF) is a metabolic disease in dairy cows around parturition. The clinical lead sign is muscular paresis leading in severe cases to paralysis of the affected animal. Multiparturient animals of high performing dairy breeds are most likely to be affected and have a high probability of recurrence. An acute drop in blood calcium levels causes the disease when the demand for calcium at the onset of lactation exceeds the ability to replete blood calcium levels through mobilization from bone and intestinal uptake. With the understanding of the underlying mechanism, calcium supply management and vitamin D supplementation became prime candidates for MF prevention and therapy. Several strategies have been developed for MF prevention. Application of the active form of Vitamin D, 1,25(OH)2D3, was found to prevent MF effectively. In order to prevent a delayed hypocalcemia, which was occasionally seen after stopping the treatment with 1,25(OH)2D3, a new approach was chosen by applying Solanum glaucophyllum extract (SGE), which contains 1,25(OH)2D3-glycosides, as instant-release (irSGE) in combination with slow-release (srSGE) tablets. In a first study, non-lactating cows were treated with a single bolus of either synthetic 1,25(OH)2D3, irSGE, or srSGE and the results were compared to a control group without treatment. Blood serum levels of 1,25(OH)2D3 (1,25D), calcium (Ca), phosphate (P) and magnesium (Mg) were followed for 11days and the area under the curve (AUC) was calculated. Calcium and phosphate excretion in urine were determined during 15days. While serum concentration of 1,25(OH)2D3 was back to pre-treatment level in the irSGE, srSGE and 1,25(OH)2D3 treated group within 3days, calcium and phosphate levels remained elevated for up to 9days. AUC of serum 1,25(OH)2D3 was 2.89 (1,25D), 3.13 (irSGE) and 4.21 (srSGE) times higher than control. Serum calcium levels were 1.07* (for 1.25D); 1.08* (for irSGE) and 1.12* (for srSGE) times higher than control. Serum phosphate levels were 1.20* (for 1,25D); 1.30* (for irSGE) and 1.41* (for srSGE) times higher than control, with * p<0.05. In a second field study calving cows treated with one bolus containing ir- and sr- tablets of SGE were compared to an untreated control group and to a group treated with 4 boli of commercial calcium salts. As a result, calcium serum levels increased (+19% compared to baseline) around calving after treatment with the single bolus of SGE. The single bolus of SGE lead also to an increase of serum phosphate (+31% compared to baseline). These calcium and phosphate increases were statistically significant (p<0.001) 0-24h after calving compared to the control group and to the group treated with calcium salts. The sample size of the study was too small to draw a conclusion on the effect on MF prevention. In conclusion, application of a single bolus of a SGE extract lead to an increase of serum calcium and phosphate for up to 9days and may thus have the potential to prevent a hypocalcemia and -phosphatemia, an important cause for clinical milk fever.
J Steroid Biochem Mol Biol 2017 10
PMID:Effects of a sustained release formulation of 1,25-dihydroxyvitamin D3-glycosides for milk fever prevention on serum 1,25-dihydroxyvitamin D3, calcium and phosphorus in dairy cows. 2834 73