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: Farhan J Bukhari, Hamid Moradi, Pavan Gollapudi, Hyun Ju Kim, Nosratola D Vaziri, Hamid M Said
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 26 Issue 7 Pg. 2137-44 (Jul 2011) ISSN: 1460-2385 [Electronic] England
• PMID: 21149507 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Folic Acid Transporters
• Membrane Transport Proteins
• Proton-Coupled Folate Transporter
• RNA, Messenger
• Repressor Proteins
• Rfc1 protein, rat
• Slc46a1 protein, rat
• Folic Acid
• Replication Protein C
• Thiamine

Topics

• Animals
• Biological Transport
• Blood Pressure
• Blotting, Western
• Brain (metabolism)
• Folic Acid (metabolism)
• Folic Acid Transporters (genetics, metabolism)
• Heart (physiology)
• Intestine, Small (metabolism)
• Kidney Failure, Chronic (genetics, metabolism, pathology)
• Liver (metabolism)
• Male
• Membrane Transport Proteins (genetics, metabolism)
• Proton-Coupled Folate Transporter (genetics, metabolism)
• RNA, Messenger (genetics)
• Rats
• Rats, Sprague-Dawley
• Replication Protein C (genetics, metabolism)
• Repressor Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Thiamine (metabolism)