Comparison of folic acid uptake characteristics by human placental choriocarcinoma cells at acidic and physiological pH

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Elisa Keating (Author) Other; Lemos, C (Author) Other; Azevedo, I (Author) Other; Martel, F (Author) FMUP

Journal

Title: Canadian Journal of Physiology and Pharmacology

Vol. 84

Pages: 247-255

ISSN: 0008-4212

Publisher: NRC Research Press

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 25 Citations

Other information

Authenticus ID: P-004-NC0

DOI: 10.1139/y05-129

Abstract (EN): The aim of this work was to characterize the placental uptake of folic acid from the maternal circulation. Using 2 human trophoblast cell lines (BeWo and JAR), we verified that uptake of H-3-folic acid was pH-dependent, increasing significantly with decreasing extracellular pH. In BeWo cells, uptake of 3 H-folic acid at pH 5.5 was (i) Na+-independent; (h) inhibited by folic acid, 5-methyltetrahydrofolate (5-MTHF), and methotrexate (MTX); (iii) inhibited by the anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulplionic acid (DIDS) and 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS); (iv) inhibited by the proton ionophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP); (v) not inhibited by blockers of receptor-mediated endocytosis (cytochalasin D and monensin); (vi) trans-inhibited by MTX and folic acid; and (vii) not affected by an anti-reduced folate transporter-1 (RFC) antibody. At pH 7.5, uptake of 3H-folic acid was (i) Na+-independent; (ii) inhibited by folic acid and MTX, but not by 5-MTHF; (iii) inhibited by SITS, but not by DIDS; (iv) not affected by FCCP; (v) inhibited by monensin (but not by cytochalasin D); (vi) trans-inhibited by folic acid (but not by MTX); and (vii) inhibited by an anti-PFC antibody. In conclusion, in BeWo cells, both RFC and receptor-mediated endocytosis seem to be involved in 3H-folic acid uptake at pH 7.5, whereas at pH 5.5, RFC and (or) a low pH-operating transporter distinct from RFC are involved.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9