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.
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: Carolina Rosa Gioda; Tatiane de Oliveira Barreto; Thales Nicolau Prímola-Gomes; Daniel Carvalho de Lima; Paula Peixoto Campos; Luciano dos Santos Aggunn Capettini; Sandra Lauton-Santos; Anilton César Vasconcelos; Cândido C Coimbra; Virginia Soares Lemos; Jorge L Pesquero; Jader S Cruz Journal: Am J Physiol Heart Circ Physiol Date: 2010-03-19 Impact factor: 4.733
Authors: Victor Soukoulis; Jamil B Dihu; Michael Sole; Stefan D Anker; John Cleland; Gregg C Fonarow; Marco Metra; Evasio Pasini; Theresa Strzelczyk; Heinrich Taegtmeyer; Mihai Gheorghiade Journal: J Am Coll Cardiol Date: 2009-10-27 Impact factor: 24.094
Authors: Alaa Alkhalaf; Nanne Kleefstra; Klaas H Groenier; Henk J G Bilo; Reinold O B Gans; Peter Heeringa; Jean L Scheijen; Casper G Schalkwijk; Gerjan J Navis; Stephan J L Bakker Journal: PLoS One Date: 2012-07-06 Impact factor: 3.240