| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS
Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, and the Albert Einstein Cancer Research Center, Bronx, New York
Submitted 30 June 2004 ; accepted in final form 17 September 2004
Intestinal folate transport has been well characterized, and rat small intestinal epithelial (IEC-6) cells have been used as a model system for the study of this process on the cellular level. The major intestinal folate transport activity has a low-pH optimum, and the current paradigm is that this process is mediated by the reduced folate carrier (RFC), despite the fact that this carrier has a neutral pH optimum in leukemia cells. The current study addressed the question of whether constitutive low-pH folate transport activity in IEC-6 cells is mediated by RFC. Two independent IEC-6 sublines, IEC-6/A4 and IEC-6/PT1, were generated by chemical mutagenesis followed by selective pressure with antifolates. In IEC-6/A4 cells, a premature stop resulted in truncation of RFC at Gln420. A green fluorescent protein (GFP) fusion with the truncated protein was not stable. In IEC-6/PT1 cells, Ser135 was deleted, and this alteration resulted in the failure of localization of the GFP fusion protein in the plasma membrane. In both cell lines, methotrexate (MTX) influx at neutral pH was markedly decreased compared with wild-type IEC-6 cells, but MTX influx at pH 5.5 was not depressed. Transient transfection of the GFP-mutated RFC constructs into RFC-null HeLa cells confirmed their lack of transport function. These results indicate that in IEC-6 cells, folate transport at neutral pH is mediated predominantly by RFC; however, the folate transport activity at pH 5.5 is RFC independent. Hence, constitutive folate transport activity with a low-pH optimum in this intestinal cell model is mediated by a process entirely distinct from that of RFC.
folic acid; folate absorption; methotrexate
This article has been cited by other articles:
|
|
 |
|
  J. J. Eloranta, C. Hiller, S. Hausler, B. Stieger, and G. A. Kullak-Ublick Vitamin D3 and Its Nuclear Receptor Increase the Expression and Activity of the Human Proton-Coupled Folate Transporter Mol. Pharmacol., November 1, 2009; 76(5): 1062 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Qiu, S. H. Min, M. Jansen, U. Malhotra, E. Tsai, D. C. Cabelof, L. H. Matherly, R. Zhao, M. H. Akabas, and I. D. Goldman Rodent intestinal folate transporters (SLC46A1): secondary structure, functional properties, and response to dietary folate restriction Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1669 - C1678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Thwaites and C. M. H. Anderson H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine Exp Physiol, July 1, 2007; 92(4): 603 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chattopadhyay, R. G. Moran, and I. D. Goldman Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications Mol. Cancer Ther., February 1, 2007; 6(2): 404 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Balamurugan and H. M. Said Role of reduced folate carrier in intestinal folate uptake Am J Physiol Cell Physiol, July 1, 2006; 291(1): C189 - C193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chattopadhyay, R. Zhao, S. A. Krupenko, N. Krupenko, and I. D. Goldman The inverse relationship between reduced folate carrier function and Pemetrexed activity in a human colon cancer cell line. Mol. Cancer Ther., February 1, 2006; 5(2): 438 - 449. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
