title: Effect of chronic kidney disease on the expression of thiamin and folic acid transporters.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is associated with significant cardiovascular, neurological and metabolic complications. Thiamin and folate are essential for growth, development and normal cellular function, and their uptake is mediated by regulated transport systems. While plasma folate and thiamin levels are generally normal in patients with CKD, they commonly exhibit features resembling vitamin deficiency states. Earlier studies have documented impaired intestinal absorption of several B vitamins in experimental CKD. In this study, we explored the effect of CKD on expression of folate and thiamin transporters in the key organs and tissues.
  
  
  METHODS
  Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy or sham operation and observed for 12 weeks. Plasma folate and thiamin concentrations and gene expression of folate (RFC, PCFT) and thiamin transporters (THTR-1 and THTR-2) were determined in the liver, brain, heart and intestinal tissues using real-time PCR. Hepatic protein abundance of these transporters was determined using western blot analysis.
  
  
  RESULTS
  Plasma folate and thiamin levels were similar between the CKD and the control groups. However, expressions of both folate (RFC and PCFT) and thiamin (THTR-1, THTR-2) transporters were markedly reduced in the small intestine, heart, liver and brain of the CKD animals. Liver protein abundance of folate and thiamin transporters was significantly reduced in the CKD animals when compared with the sham-operated controls. Furthermore, we found a significant reduction in mitochondrial folate and thiamin transporters in the CKD animals.
  
  
  CONCLUSIONS
  CKD results in marked down-regulation in the expression of folate and thiamin transporters in the intestine, heart, liver and brain. These events can lead to reduced intestinal absorption and impaired cellular homeostasis of these essential micronutrients despite their normal plasma levels.
authors.affiliation: Department of Medical Research, VA Medical Center, 5901 East 7th St, Long Beach, CA 90822, USA.
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Bukhari
authors.forename: Hamid
authors.initials: H
authors.lastname: Moradi
authors.forename: Pavan
authors.initials: P
authors.lastname: Gollapudi
authors.forename: Hyun
authors.initials: H
authors.lastname: Ju Kim
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D058972:Folic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000502:physiology; D007421:Intestine, Small / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D058979:Proton-Coupled Folate Transporter / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051818:Replication Protein C / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013831:Thiamine / Q000378:metabolism*
chemical_list: D058972:Folic Acid Transporters; D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; D012333:RNA, Messenger; D012097:Repressor Proteins; C113967:Rfc1 protein, rat; C525126:Slc46a1 protein, rat; D005492:Folic Acid; D051818:Replication Protein C; D013831:Thiamine