Disease relevance of UF

• The invariant presence of UF binding components in sites of hematopoiesis during fetal development suggests that mechanism(s) unrelated to specific uptake of UF are responsible for neonatal anemia [1].
• However, unlike reduced FIV Uf, the pink, high molecular form does not revert to purple, nor does it show loss of EPR signal and phosphatase activity in the presence of oxygen [2].
• The type 5, acid phosphatase from spleen of humans with hairy cell leukemia. Purification, properties, immunological characterization, and comparison with porcine uteroferrin [3].
• Analysis of uterine flushings with two-dimensional PAGE procedures indicated advanced uteroferrin-associated glycoprotein secretion from the horn that contained more-developed embryos [4].
• Concurrent treatment of pigs with uteroferrin reduced (P < 0.05) the rate of 5-FU-induced leukocytopenia (44 vs 77 +/- 7% decline from baseline on day 3) and enhanced (P < 0.05), the recovery from 5-FU on days 10 and 12 postinfusion [5].

High impact information on UF

• Uteroferrin is an iron-containing, progesterone-induced, acid phosphatase that is secreted in large amounts by the uterine endometrium of pigs [6].
• Uteroferrin has N-asparagine-linked high-mannose-type oligosaccharides that contain mannose 6-phosphate [6].
• On uteroferrin, however, the majority of the phosphate is in single diester linkages between the mannose and a covering N-acetylglucosamine [6].
• Uteroferrin and intracellular tartrate-resistant acid phosphatases are the products of the same gene [7].
• Although no full-length cDNA for the former were isolated, a TRAP cDNA of 1.1 kilobases was identical in nucleotide sequence to a Uf cDNA (1.42 kilobases) in the region of overlap, which included the entire 3'-end of the transcript and most of the open reading frame [7].

Chemical compound and disease context of UF

• The visible absorption spectrum, EPR signal, and acid phosphatase activity of Uf in FIII are almost identical to those of FIV Uf after the latter has been reduced by 2-mercaptoethanol [2].
• In uterine flushings, total recoverable protein (p less than 0.05), uteroferrin (p less than 0.01), leucine aminopeptidase (p less than 0.05), calcium (p less than 0.03), sodium (p less than 0.01), and potassium (p less than 0.05) increased between 12 and 24 h following EV treatment.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• These same polypeptides, including the putative uteroferrin, were also present in uterine flushings from pregnant animals until Day 20, and in flushings from ovariectomized mares treated with progesterone but not in those given only oestradiol-17 beta [9].
• Recovered flushings were analysed for total luminal protein, retinol binding protein, uteroferrin, prostaglandin E and prostaglandin F [10].
• Blastocyst size was measured and concentrations of E2, retinol, uteroferrin, insulin-like growth factor-I (IGF-I), uterine plasmin/trypsin inhibitor (UPTI) and protein in uterine flushings were quantified [11].

Biological context of UF

• Catalase and superoxide dismutase had no effect on UF-induced lipid peroxidation in fetal liver membranes [12].
• For treatments 7 through 10, membranes were preincubated (0 degrees C, 3 h) with either 7) no treatment, 8) 50 microM fetuin, 9) 50 microM holoretinol binding protein (holoRBP: retinol binding protein [HoloRBP] with retinol bound), or 10) 50 microM apoRBP (RBP with no retinol bound) followed by incubation with 50 microM ASC + 100 microM UF [12].
• Finally, Southern hybridization analysis with two probes specific for exons 1 and 2 of the Uf gene strongly suggested the presence of only a single gene for acid phosphatases of this class in the pig [7].
• TRAP purified from porcine spleen also had an NH2-terminal amino acid sequence that corresponded to that of Uf purified from uterine secretions and was also similar in sequence to intracellular TRAP isolated from tissues of other species, including ones from human osteoclastomas and spleen [7].
• The hybridization signals revealed that the uteroferrin gene (ACP5) is located on swine chromosome 2q12-->q21 [13].

Anatomical context of UF

• Combined ASC and UF caused a large increase (p < 0.05) in TBARS in all membranes except Day 30 placental membranes [12].
• The functional relevance of this DNA-binding protein in the control of UF gene transcription in the endometrium is discussed [14].
• It is concluded that the difference in trafficking between a secreted TRAP, such as Uf, and TRAP located in lysosomes is not the result of distinctive primary sequence of the polypeptides and that the variability within species ascribed to such enzymes is most likely the result of minor posttranslational changes [7].
• Expression of the gene for the porcine transplacental iron transport protein uteroferrin (UF) is largely restricted to the uterus, where it is differentially regulated by estrogen (E) and progesterone (P) [15].
• The increase in UF promoter activity with BTEB was mimicked by PR in a P-dependent manner in both cell lines [16].

Associations of UF with chemical compounds

• Uteroferrin is an iron-binding glycoprotein, which is abundantly synthesized in porcine uterine glandular endometrium and believed to be involved in maternal/fetal iron transport [17].
• cDNA sequence, gene organization, and progesterone induction of mRNA for uteroferrin, a porcine uterine iron transport protein [18].
• The steady-state level of uteroferrin mRNA is enhanced by progesterone but not by estrogen alone, although the extent of progesterone induction is lower than at midgestation [18].
• The simple organization of the uteroferrin gene, which contrasts with those of the transferrin gene family, and the progesterone induction of uteroferrin mRNA expression suggest that, although this protein may have evolved in a manner distinct from other iron binding proteins, its regulation by steroid hormones may be similar [18].
• Administration of E to gilts on Day 11 of the cycle slightly diminished UF mRNA levels at 1 h post-E; had no effect at 6, 12, and 24 h post-E; and increased levels of secreted UF in uterine luminal fluids 24 h post-E [19].

Other interactions of UF

• Myometrium and endometrium expressed comparable levels of UF and ALP mRNAs within Days 75 or 105, but placenta did not express detectable levels of mRNA for either protein [19].
• Tissues from all all except the cyclic animals released an identical group of polypeptides into the culture medium: the major radioactive products were 4 acidic polypeptides of low molecular weight and several basic proteins, which included the purple phosphatase uteroferrin, and lysozyme [20].
• Total recoverable glucose (P less than 0.01), PGF-2 alpha (P less than 0.02), uteroferrin (P less than 0.01) and specific activity of uteroferrin (P less than 0.001) were increased by prolactin and oestradiol, but not oestradiol alone [21].
• Treatments had no effect on uterine content of uteroferrin or secreted folate-binding protein in uterine flushings obtained on d 15 of pregnancy [22].

Analytical, diagnostic and therapeutic context of UF

• The genomic fragment thus cloned was examined by Southern blot and sequence analysis which demonstrated that it contained at least a part of the uteroferrin gene [13].
• Assignment of the uteroferrin gene (ACP5) to swine chromosome 2q12-->q21 by fluorescence in situ hybridization [13].
• Affinity cross-linking of 125I-UF to liver membrane-associated binding sites and subsequent analysis by gel electrophoresis and autoradiography demonstrated a single labeled protein complex of Mr 58,000 and 87,000 under denaturing and nondenaturing conditions, respectively [1].
• (Pyrz, J. W., Sage, J. T., Debrunner, P. G., and Que, Jr., L. (1986) J. Biol Chem. 261, 11015-11020) using Mossbauer spectroscopy and dithionite-reduced 57Fe-reconstituted uteroferrin [23].
• Titration of purple uteroferrin with two reducing equivalents of ferrous ion doubles the intensity of its g' = 1.74 EPR signal while inducing only minor changes in spectral characteristics [24].

References