Functional Characterization of Folate Transport Proteins in Staten’s Seruminstitut Rabbit Corneal Epithelial Cell Line
Jwala Jwala,Sai H.S. Boddu,Durga K. Paturi,Sujay Shah,Sylvia B. Smith,Dhananjay Pal,Ashim K. Mitra +6 more
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TLDR
This work demonstrated the functional and molecular presence of FR-alpha and PCFT in SIRC epithelial cell line and found the uptake process was found to be dependent on pH, sodium ions, chloride ions, temperature, and energy.Abstract:
Purpose:The overall objective of this study was to investigate and characterize the expression of folate transport proteins in Staten’s Seruminstitut rabbit corneal (SIRC) epithelial cell line.Methods: [3H]Folic acid uptake was studied with respect to time, pH, temperature, sodium, and chloride ion dependency. Inhibition studies were conducted with structural analogs, vitamins, and metabolic inhibitors. [3H]Folic acid uptake was also determined with varying concentrations of cold folic acid. Uptake kinetics was studied in the presence of various modulators of intracellular regulatory pathways, protein kinases A and C (PKA and PKC), protein tyrosine kinase (PTK), and calcium-calmodulin modulators. Ex vivo corneal permeability studies were carried out with [3H]folic acid in the presence and absence of 1 mM cold folic acid.Results: Linear increase in [3H]folic acid uptake was observed over 30 min. The process followed saturation kinetics with apparent Km of 14.2 ± 0.2 nM, Vmax of (1.5 ± 0.1)*10−5 micro.moles...read more
Citations
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Ocular Drug Delivery
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Folic acid deficiency and vision: a review.
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Prodrugs and nanomicelles to overcome ocular barriers for drug penetration.
TL;DR: This article focuses on enhancing drug absorption across the corneal and conjunctival epithelium, where transporter targeted prodrug formulations and nanomicellar strategy is proven to enhance the drug permeation of therapeutic agents across various ocular barriers.
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Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics
Anne L Kunkler,Elaine M Binkley,Dimosthenis Mantopoulos,Andrew J Hendershot,Matthew P Ohr,Kari Kendra,Frederick H. Davidorf,Colleen M. Cebulla +7 more
TL;DR: Cases of permanent visual loss were observed; yet, in the majority of side effects, they improved with topical therapy and/or holding the medication, and further research is needed to elucidate the incidence and the pathophysiology of these side effects.
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Differential expression of folate receptor-alpha, sodium-dependent multivitamin transporter, and amino acid transporter (B (0, +)) in human retinoblastoma (Y-79) and retinal pigment epithelial (ARPE-19) cell lines.
Jwala Jwala,Ramya Krishna Vadlapatla,Aswani Dutt Vadlapudi,Sai Hanuman Sagar Boddu,Dhananjay Pal,Ashim K. Mitra +5 more
TL;DR: This work demonstrated for the first time the higher expression and affinity of FR-α, SMVT, and B ((0, +)) mRNA levels in retinoblastoma (Y-79) cells compared with retinal pigment epithelial (ARPE-19) cells.
References
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Membrane transport of folates.
TL;DR: Many of the key in vitro findings on the properties of antifolate transporters are now beginning to be extended to patient specimens, thus setting the stage for understanding response to these drugs in the clinical setting at the molecular level.
Journal ArticleDOI
The molecular identity and characterization of a Proton-coupled Folate Transporter--PCFT; biological ramifications and impact on the activity of pemetrexed.
Rongbao Zhao,I. David Goldman +1 more
TL;DR: The key role this transporter plays in intestinal folate absorption has been confirmed by the demonstration of a mutation in this gene in the rare autosomal recessive disorder, hereditary folate malabsorption.
Journal ArticleDOI
Functional characterization of PCFT/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model
Katsuhisa Inoue,Yasuhiro Nakai,Sayaka Ueda,Shunsuke Kamigaso,Kinya Ohta,Mai Hatakeyama,Yayoi Hayashi,Masaki Otagiri,Hiroaki Yuasa +8 more
TL;DR: This study is the first to clone rPCFT/HCP1, and it successfully provided several lines of evidence that indicate its role as the molecular entity of the carrier-mediated intestinal folate transport system.
Journal ArticleDOI
Identification of two putative novel folate receptor genes in humans and mouse
TL;DR: A 'database mining' strategy to detect novel folate receptors (FR) identified two potential novel members in the mouse and human, suggesting a potential role in the immune system and an alternatively spliced variant or an additional FR pseudogene.
Journal ArticleDOI
Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system.
TL;DR: This new system provides a rapid, accurate, and economical option for passive permeability determination, and appears to be applicable to the proposed Biopharmaceutics Classification System (BCS).
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