title: Adaptive transport of folic acid across renal epithelia in folate-deficient rats.
abstract: Folate (vitamin B(9)) is an essential vitamin for a wide spectrum of biochemical reactions; however, unlike bacteria and plants, mammals are devoid of folate biosynthesis and thus must obtain this cofactor from exogenous sources. The activities of folate transporters on the kidneys play an important role in conserving folate excretion and reabsorption across the apical membrane of the renal proximal tubules. The different transport system activities may become identifiable in response to external stimuli, such as folate availability and exposure to chemotherapeutic agents. We have explored the effect of folate deficiency on the activity and expression of folate transporters in rat kidneys. Wistar rats were fed a folate-containing diet (2 mg folic acid kg(-1) diet) or a folic acid-free diet over a 3-month period, and mechanisms of folate transport were studied in renal brush border membrane vesicles and basolateral membrane vesicles. The renal folate uptake process is saturable and pH dependent, and it involves the folate receptor and reduced folate carrier (RFC) systems and possibly the proton coupled folate transporter (PCFT) system. We found that folate deficiency increased the renal brush border membrane and basolateral folate uptake by increasing the number of transporter molecules. The observed up-regulation of mRNA expression was also associated with a significant increase in RFC and PCFT expression at the protein level.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
authors.forename: Nissar Ahmad
authors.initials: NA
authors.lastname: Wani
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004848:Epithelium / Q000378:metabolism; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000235:genetics / Q000378:metabolism*; D058972:Folic Acid Transporters / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D058979:Proton-Coupled Folate Transporter / Q000235:genetics / Q000378:metabolism; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D058978:Reduced Folate Carrier Protein / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D058972:Folic Acid Transporters; D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; D050683:R-SNARE Proteins; D012333:RNA, Messenger; D058978:Reduced Folate Carrier Protein; C525126:Slc46a1 protein, rat; D005492:Folic Acid