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• W2025366504 abstract "Drug delivery to the retina is a challenging task owing to its complex physiology and presence of the blood-retinal barrier (BRB), which regulates the permeation of substances from blood into the retina. Transporter-targeted drug delivery has become a clinically significant drug-delivery approach for enhancing the bioavailability of various drugs. Different nutrient transporters have been reported to be expressed on the retina. Riboflavin (vitamin B2), an essential nutritional vitamin for the development and maintenance of the surface structures and functions of epithelial cells of the ocular tissues, must be acquired from retinal or choroidal blood supply. The uptake mechanism, cellular translocation, and major regulatory pathways of riboflavin uptake into retina are poorly understood. Therefore, the aim of this study was to investigate the presence of a riboflavin transporter and delineate uptake and intracellular trafficking of riboflavin in the human-derived retinoblastoma cell line (Y-79), a model for neural retina. Uptake characteristics of [3H]riboflavin in Y-79 cells were found to be (1) linear with time over 10 min of incubation; (2) temperature- and energy-dependent; (3) sodium, chloride-, and pH-independent; (4) concentration dependence with an apparent K(m) of 19.21 +/- 0.37 nM and V(max) of 6.98 +/- 0.30 pmol/min/mg protein; (5) inhibited by the structural analogs (lumiflavin and lumichrome) but not by the structurally unrelated vitamins; and (6) uptake of [3H]riboflavin was trans-stimulated by the intracellular riboflavin. Neither protein kinase C- nor protein tyrosine kinase-mediated pathways were involved in regulating riboflavin uptake. However, protein kinase A pathway activators (IBMX and forskolin) and inhibitors (H-89) and Ca2+/calmodulin pathways appeared to play important roles in the regulation of riboflavin uptake in Y-79 cells through significant reduction in V(max) (39%) and significant increase in K(m) (112%) of the uptake process. These studies demonstrated, for the first time, the existence of a specialized carrier-mediated system for riboflavin uptake in human-derived retinoblastoma cells. The system appears to be regulated by protein kinase A and Ca2+/calmodulin pathways. Being a high-affinity low-capacity transport system, the presence of this transporter on the retina may be suitable for the design of transporter-targeted prodrugs to achieve enhanced permeability for highly potent, but poorly bioavailable, compounds where a small increase in the bioavailability could result in a significant increase in therapeutic response." @default.
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• W2025366504 date "2005-08-01" @default.
• W2025366504 modified "2023-10-16" @default.
• W2025366504 title "Identification and Functional Characterization of Riboflavin Transporter in Human-Derived Retinoblastoma Cell Line (Y-79): Mechanisms of Cellular Uptake and Translocation" @default.
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• W2025366504 doi "https://doi.org/10.1089/jop.2005.21.275" @default.
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