scholarly journals α Isoforms of soluble and membrane-linked folate-binding protein in human blood

2008 ◽  
Vol 28 (3) ◽  
pp. 153-160 ◽  
Author(s):  
Mimi Høier-Madsen ◽  
Jan Holm ◽  
Steen I. Hansen
Keyword(s):  
Human Blood ◽  
Binding Protein ◽  
Folate Receptor ◽  
Gel Filtration ◽  
Secretory Protein ◽  
Erythrocyte Membranes ◽  
Neutrophil Granulocytes ◽  
Biological Degradation ◽  
Folate Binding Protein ◽  
Mature Neutrophil

The high-affinity FBP/FR (folate-binding protein/folate receptor) is expressed in three isoforms. FRα and FRβ are attached to cell membranes by hydrophobic GPI (glycosylphosphatidylinositol) anchors, whereas FBPγ is a secretory protein. Mature neutrophil granulocytes contain a non-functional FRβ on the surface, and, in addition, nanomolar concentrations of a secretory functional FBP (29 kDa) can be present in the secondary granules. A statistically significant correlation between the concentrations of functional FBP, probably a γ isoform, in granulocytes and serum supported the hypothesis that serum FBP (29 kDa) mainly originates from neutrophils. The presence of FBP/FRα isoforms were established for the first time in human blood using antibodies specifically directed against human milk FBPα. The α isoforms identified on erythrocyte membranes, and in granulocytes and serum, only constituted an almost undetectable fraction of the functional FBP. The FBPα in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBPα (>120 kDa), which could represent receptor fragments from decomposed erythrocytes and granulocytes. The soluble FBPs may exert bacteriostatic effects and protect folates in plasma from biological degradation, whereas FRs on the surface of blood cells could be involved in intracellular folate uptake or serve as signal proteins. The latter receptors have also been used for therapeutic targeting in malignancy.

Characterization of a High-Affinity Folate Receptor in Normal and Malignant Human Testicular Tissue

1999 ◽  
Vol 19 (6) ◽  
pp. 571-580 ◽  
Author(s):  
Jan Holm ◽  
Steen Ingemann Hansen ◽  
Mimi Høier-Madsen ◽  
Thomas Broe Christensen ◽  
Carl W. Nichols
Keyword(s):  
Human Milk ◽  
G Protein ◽  
Radioligand Binding ◽  
Binding Protein ◽  
Folate Receptor ◽  
Testicular Tissue ◽  
Hydrophobic Membrane ◽  
Folate Binding Protein ◽  
High Affinity ◽  
Triton X

We have characterized the folate receptor in normal and malignant tissue from male gonads. Radioligand binding displayed characteristics typical of other folate receptors. Those included a high-affinity type of binding (K = 1010 M−1), apparent positive cooperativity changing into non-cooperativity at low receptor concentrations, a tendency to increased binding affinity with decreasing receptor concentrations, a slow dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition by folates, in particular oxidized forms. The gel filtration profile of Triton X-100 solubilized tissue contained a 25 and 100 kDa peak of radioligand-receptor. The latter peak could represent receptor equipped with a hydrophobic membrane anchor that inserts into Triton X-100 micelles. The concentration of radiolabelled receptor ranged from 0.41 nmol/g protein to 1.68 nmol/g protein in specimens of normal testicular tissue from patients with prostatic carcinomas and from 1.54 nmol/g protein to 3.82 nmol/g protein in testicular tissue from young individuals. Compared to normal testicular tissue the concentration of receptor in seminoma tissue was low (0.38–1.27 nmol/g protein) but showed a higher degree of immunoreactivity in the presence of antibodies against human milk folate binding protein as evidenced by ELISA and immunohistochemistry data. Hence a folate receptor isoform homologous to human milk folate binding protein is apparently expressed in seminomas where the total expression of receptor, however, seems to be lower than in normal testicles.

Role of the membrane-associated folate binding protein (folate receptor) in methotrexate transport by human KB cells

1989 ◽  
Vol 274 (2) ◽  
pp. 327-337 ◽  
Author(s):  
John C. Deutsch ◽  
Patrick C. Elwood ◽  
Raul M. Portillo ◽  
Michelle G. Macey ◽  
J.Fred Kolhouse
Keyword(s):  
Binding Protein ◽  
Folate Receptor ◽  
Kb Cells ◽  
Folate Binding Protein

scholarly journals A Bibliometric Analysis of Folate Receptor Research

2020 ◽  
Author(s):  
Cari Didion ◽  
Walter Henne
Keyword(s):  
Bibliometric Analysis ◽  
Web Of Science ◽  
Binding Protein ◽  
Folate Receptor ◽  
Citation Rate ◽  
Time Frame ◽  
Folate Binding Protein ◽  
Average Citation ◽  
The Us ◽  
Receptor Research

Abstract Background The objective of this study is to conduct a comprehensible bibliometric analysis of the entire field of folate receptor research. Methods A Web of Science search was performed on folate receptor or folate binding protein (1969-to June 28, 2019). The following information was examined: publications per year, overall citations, top 10 authors, top 10 institutions, top 10 cited articles, top 10 countries, cc-author collaborations and key areas of research. Results In total, 3248 documents for folate receptor or folate binding protein were retrieved for the study years outlined in the methods section search query. The range was 1 per year in 1969 to 264 for the last full year studied (2018). A total of 123,720 citations for the 3,248 documents retrieved represented a mean citation rate per article of 38.09 and range of 1667 citations (range 0 to 1667). Researchers in 71 countries authored publications analyzed in this study. The US was the leader in publications and had the highest ranking institution. The top 10 articles have been cited 7270 times during the time frame of this study. The top cited article had an average citation rate of 110 citations per year. Network maps revealed considerable co-authorship among several of the top 10 authors. Conclusion Our study presents several important insights into the features and impact of folate receptor research. To our knowledge, this is the first bibliometric analysis of folate receptor.

scholarly journals A Bibliometric Analysis of Folate Receptor Research: A comprehensive bibliometric analysis of the entire field of Folate Receptor Research

2020 ◽  
Author(s):  
Cari Didion ◽  
Walter Henne
Keyword(s):  
Bibliometric Analysis ◽  
Binding Protein ◽  
Folate Receptor ◽  
Citation Rate ◽  
Time Frame ◽  
Folate Binding Protein ◽  
Entire Field ◽  
Average Citation ◽  
The Us ◽  
Receptor Research

Abstract Background The objective of this study is to conduct a comprehensible bibliometric analysis of the entire field of folate receptor research. Methods A Web of Science search was performed on folate receptor or folate binding protein (1969-to June 28, 2019). The following information was examined: publications per year, overall citations, top 10 authors, top 10 institutions, top 10 cited articles, top 10 countries, cc-author collaborations and key areas of research. Results In total, 3248 documents for folate receptor or folate binding protein were retrieved for the study years outlined in the methods section search query. The range was 1 per year in 1969 to 264 for the last full year studied (2018). A total of 123,720 citations for the 3,248 documents retrieved represented a mean citation rate per article of 38.09 and range of 1667 citations (range 0 to 1667). Researchers in 71 countries authored publications analyzed in this study. The US was the leader in publications and had the highest ranking institution. The top 10 articles have been cited 7270 times during the time frame of this study. The top cited article had an average citation rate of 110 citations per year. Network maps revealed considerable co-authorship among several of the top 10 authors. Conclusion Our study presents several important insights into the features and impact of folate receptor research. To our knowledge, this is the first bibliometric analysis of folate receptor.

Characterization of a High Affinity Folate Binding Protein in Porcine Serum: Ionic Charge, Concentration—Dependent Polymerization and Ligand Binding Mechanism

2003 ◽  
Vol 23 (5-6) ◽  
pp. 339-351 ◽  
Author(s):  
Jan Holm ◽  
Steen Ingemann Hansen
Keyword(s):  
Affinity Chromatography ◽  
Binding Protein ◽  
Gel Filtration ◽  
Competitive Inhibitor ◽  
Exchange Chromatography ◽  
Ionic Charge ◽  
Folate Binding Protein ◽  
Porcine Serum ◽  
Hill Coefficients ◽  
Triton X

The folate binding protein in porcine serum, present at concentrations of 50-100 nM, is cationic at near neutral pH as evidenced by ion exchange chromatography. The gel filtration profile of the protein isolated from porcine serum by methotrexate affinity chromatography exhibited one peak at 48 kDa and an additional peak of 91 kDa at higher protein concentrations. This could suggest the involvement of concentration-dependent polymerization phenomena. Binding of [3H] folate was of a high-af.nity type with upward convex Scatchard plots and Hill coefficients >1.0 indicative of apparent positive cooperativity. However, binding to protein isolated from porcine serum after affinity chromatography was biphasic (high/low-affinity) in the absence of Triton X-100, 1 g/1. These findings which are similar to those reported for purified milk folate binding proteins are consistent with a model predicting association between unliganded and liganded monomers to weak-ligand affinity heterodimers. Amphiphatic substances, e.g. Triton X-100, form micelles which could separate hydrophobic unliganded monomers from hydrophilic liganded monomers (monomers are hydrophilic in the liganded state) thereby preventing heterodimerization. The folate analogue N10 methyl folate was a potent and competitive inhibitor of [3H] folate binding to the folate binding protein, and moreover changed the binding type to apparent negative cooperativity.

Evidence that the low-affinity folate-binding protein in erythrocyte hemolysate is identical to hemoglobin.

1981 ◽  
Vol 27 (7) ◽  
pp. 1247-1249 ◽  
Author(s):  
S I Hansen ◽  
J Holm ◽  
J Lyngbye
Keyword(s):  
Anion Exchange ◽  
Salt Concentration ◽  
Binding Protein ◽  
Gel Filtration ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Chromatographic Behavior ◽  
Folate Binding Protein ◽  
Low Salt

Abstract Gel filtration studies on erythrocyte hemolysate demonstrated the presence of a folate binding protein, apparently of the low-affinity type, that co-elutes with hemoglobin. Further, the folate binder eluted with a low salt concentration after DEAE-Sepharose CL-6B anion-exchange chromatography of erythrocyte hemolysate at pH 6.3. The chromatographic behavior of hemoglobin labeled with [3H]folate was so similar to that of the present binder as to suggest that the folate binder in erythrocytes is in fact hemoglobin.

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