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

J Ocul Pharmacol Ther. 2012 Jun;28(3):237-44. doi: 10.1089/jop.2011.0155. Epub 2012 Feb 3.

Abstract

Purpose: The overall objective of this study was to investigate the differential expression of folate receptor-alpha (FR-α), sodium-dependent multivitamin transporter (SMVT), and amino acid transporter [B ((0, +))] in retinoblastoma (Y-79) and retinal pigment epithelial (ARPE-19) cells.

Methods: Polymerase chain reaction (PCR) analysis was performed to confirm the existence of FR-α, SMVT, and B ((0, +)) in Y-79 and ARPE-19 cell lines. Quantitative real-time PCR was also performed to determine the relative expression of FR-α, SMVT, and B ((0, +)) at mRNA level in these cell lines. Quantitative uptake of [(3)H] Folic acid, [(3)H] Biotin, and [(14)C] Arginine was studied in Y-79 and ARPE-19 cells. Further, saturation kinetics of [(3)H] Folic acid, [(3)H] Biotin, and [(14)C] Arginine was performed in the presence of various concentrations of respective cold substrates to determine the kinetic parameters (K(m) and V(max)) in Y-79 and ARPE-19 cells.

Results: PCR analysis had confirmed the existence of FR-α, SMVT, and B ((0, +)) in Y-79 and ARPE-19 cells. Quantitative real-time PCR analysis had shown significantly higher expression of FR-α, SMVT, and B ((0, +)) mRNA levels in Y-79 cells compared with ARPE-19 cells. Quantitative uptake of [(3)H] Folic acid, [(3)H] Biotin, and [(14)C] Arginine was found to be significantly higher in Y-79 cells relative to ARPE-19 cells. [(3)H] Folic acid uptake process followed saturation kinetics with apparent K(m) of 8.29 nM and V(max) of 393.47 fmol/min/mg protein in Y-79 cells and K(m) of 80.55 nM and V(max) of 491.86 fmol/min/mg protein in ARPE-19 cells. [(3)H] Biotin uptake process also displayed saturation kinetics with K(m) of 8.53 μM and V(max) of 14.12 pmol/min/mg protein in Y-79 cells and K(m) of 138.25 μM and V(max) of 38.85 pmol/min/mg protein in ARPE-19 cells. [(14)C] Arginine uptake process followed saturation kinetics with K(m) of 16.77 μM and V(max) of 348.27 pmol/min/mg protein in Y-79 cells and K(m) of 52.03 μM and V(max) of 379.21 pmol/min/mg protein in ARPE-19 cells.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / biosynthesis*
  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism
  • Arginine / metabolism
  • Biotin / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Epithelial Cells / metabolism
  • Folate Receptor 1 / biosynthesis*
  • Folate Receptor 1 / genetics
  • Folate Receptor 1 / metabolism
  • Folic Acid / metabolism
  • Gene Expression
  • Humans
  • Kinetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Retinal Neoplasms / genetics
  • Retinal Neoplasms / metabolism*
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism*
  • Retinoblastoma / genetics
  • Retinoblastoma / metabolism*
  • Symporters / biosynthesis*
  • Symporters / genetics
  • Symporters / metabolism

Substances

  • Amino Acid Transport Systems
  • Folate Receptor 1
  • RNA, Messenger
  • Symporters
  • biotin transporter
  • Biotin
  • Folic Acid
  • Arginine