Topic
Folic acid binding
About: Folic acid binding is a research topic. Over the lifetime, 63 publications have been published within this topic receiving 4468 citations.
Papers published on a yearly basis
Papers
TL;DR: Little is known about the tissue specificities of FR β and FR‐α, but there is no report on the relative expression of FR‐β in any tissue other than in placenta.
Abstract: Background Despite significant differences in ligand binding between the two known isoforms of the human membrane folate receptor (FR), designated herein as FR-beta (placenta) and FR-alpha (placenta, KB cells), little is known about their tissue specificities, and there is no report on the relative expression of FR-beta in any tissue other than in placenta. Methods The mRNA for each FR isoform in a wide variety of normal fetal and adult tissue explants, primary normal cell cultures, malignant tumor explants, and established tumor cell lines was estimated by a polymerase chain reaction assay. Total receptor levels were estimated by a [3H] folic acid binding assay. Results Both the FR isoforms were expressed in fetal as well as adult tissues. Normal tissues generally expressed low to moderate amounts of FR-beta. FR-alpha alone was expressed in normal epithelial cells and was frequently strikingly elevated in a variety of carcinomas, with the exception of squamous cell carcinomas of the head and neck. In contrast, a variety of malignant tissues of nonepithelial origin generally expressed elevated levels of FR-beta alone. Established tumor cell lines expressed FR-alpha virtually alone and did not reflect FR expression patterns in vivo. KB cells and JEG-3 cells grown at low folate concentrations further up-regulated FR-alpha but not FR-beta. Conclusions Although FR-beta is the more common isoform, FR-alpha and FR-beta are differentially regulated in normal tissues, carcinomas, nonepithelial malignancies, and immortalized cells or in response to changes in extracellular folate concentrations. The tissue specificity of FR isoforms and their elevation in malignant tissues may be a significant factor in FR-mediated folate uptake, in tissue responsiveness to promising novel antifolates, and in FR-related immunodiagnosis/immunotherapy.
967 citations
TL;DR: The results suggest that Folbp1 has a critical role in folate homeostasis during development, and that functional defects in the human homologue (FOLR1) of FolBP1 may contribute to similar defects in humans.
Abstract: Periconceptional folic acid supplementation reduces the occurrence of several human congenital malformations, including craniofacial, heart and neural tube defects1,2,3,4. Although the underlying mechanism is unknown, there may be a maternal-to-fetal folate-transport defect or an inherent fetal biochemical disorder that is neutralized by supplementation. Previous experiments have identified a folate-binding protein5,6,7 (Folbp1) that functions as a membrane receptor to mediate the high-affinity internalization and delivery of folate to the cytoplasm of the cell8,9,10. In vitro, this receptor facilitates the accumulation of cellular folate a thousand-fold relative to the media, suggesting that it may be essential in cytoplasmic folate delivery in vivo. The importance of an adequate intracellular folate pool for normal embryogenesis has long been recognized in humans11,12,13,14,15,16 and experimental animals17,18,19. To determine whether Folbp1 is involved in maternal-to-fetal folate transport, we inactivated Folbp1 in mice. We also produced mice lacking Folbp2, another member of the folate receptor family that is GPI anchored but binds folate poorly20. Folbp2–/– embryos developed normally, but Folbp1–/– embryos had severe morphogenetic abnormalities and died in utero by embryonic day (E) 10. Supplementing pregnant Folbp1+/– dams with folinic acid reversed this phenotype in nullizygous pups. Our results suggest that Folbp1 has a critical role in folate homeostasis during development, and that functional defects in the human homologue (FOLR1) of Folbp1 may contribute to similar defects in humans.
388 citations
TL;DR: A cDNA library from a human carcinoma cell line, Caco-2, which expresses the membrane form abundantly was constructed and a near full-length cDNA for the folate binder was isolated, which deduced amino acid sequence is not consistent with a typical membrane spanning domain but rather with a signal for anchoring via a glycosyl-phosphatidylinositol linkage.
Abstract: Membrane bound and soluble forms of a high-affinity folate binding protein have been found in kidney, placenta, serum, milk, and in several cell lines. The two forms have similar binding characteristics for folates, are immunologically cross-reactive and based upon limited amino acid sequence data, are nearly identical. Based upon pulse-chase experiments, a precursor-product relationship has been suggested. The membrane form has been shown to mediate the transport of folate in cells grown in physiological concentrations of folate. A function for the soluble form has not yet been identified. We constructed a cDNA library from a human carcinoma cell line, Caco-2, which expresses the membrane form abundantly. The library was screened and a near full-length cDNA for the folate binder was isolated. Transfection of COS cells with the cDNA inserted in an expression vector resulted in marked overexpression of a membrane-associated folate binder as assessed by direct binding of radiolabeled folate and by indirect immunofluorescence. The deduced amino acid sequence is not consistent with a typical membrane spanning domain but rather with a signal for anchoring via a glycosyl-phosphatidylinositol linkage. Release of the binder with a phosphatidylinositol-specific phospholipase C strongly supports this hypothesis.
258 citations
TL;DR: In this study, human FBP cDNA clones were isolated from human malignant nasopharyngeal carcinoma cell and placental cDNA libraries by means of oligonucleotide probes derived from determined internal amino acid sequences.
257 citations
15 May 2010
TL;DR: Polyelectrolyte multilayers composed of two natural polysaccharides-chitosan (Chi) and alginate (Alg) were deposited by Layer by layer assembly on top of biocompatible poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs).
Abstract: Polyelectrolyte multilayers (PEMs) composed of two natural polysaccharides-chitosan (Chi) and alginate (Alg) were deposited by Layer by layer (LbL) assembly on top of biocompatible poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs). Folic acid (FA) or FA grafted poly(ethylene glycol) (PEG–FA) were covalently bounded to the PEMs via carbodiimide chemistry. The assembly of biocompatible PEMs was monitored on planar surfaces by means of the quartz crystal microbalance with dissipation (QCM-D) technique and on top of PLGA NPs by means of ζ-potential measurements. BSA was used as model protein to characterize protein adsorption on PEMs. QCM-D showed protein deposition could not be observed on the Chi/Alg multilayer, for both Chitosan and Alginate as top layers. Finally, cellular uptake experiments were carried out by co-culture of HepG2 cells in presence of NPs. Flow Cytometry and confocal laser scanning microscopy (CLSM) were used to investigate the influence of the surface chemistry of the NPs on uptake. For the HepG2 cell line significantly less uptake of PLGA NPs coated with Chi/Alg than the bare NPs was observed but the uptake increased after attachment of FA molecules.
161 citations
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Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 1 |
| 2019 | 1 |
| 2018 | 2 |
| 2015 | 1 |
| 2013 | 1 |
| 2011 | 2 |