RESUMO
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.
Assuntos
Transportadores de Ácido Fólico/metabolismo , Ácido Fólico/metabolismo , Falência Renal Crônica/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Tiamina/metabolismo , Animais , Transporte Biológico , Pressão Sanguínea , Western Blotting , Encéfalo/metabolismo , Transportadores de Ácido Fólico/genética , Coração/fisiologia , Intestino Delgado/metabolismo , Falência Renal Crônica/genética , Falência Renal Crônica/patologia , Fígado/metabolismo , Masculino , Proteínas de Membrana Transportadoras/genética , Transportador de Folato Acoplado a Próton/genética , Transportador de Folato Acoplado a Próton/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Proteína de Replicação C/genética , Proteína de Replicação C/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We evaluated the relationship between polymorphisms in the GSTM1 and GSTT1 genes and smoking status in a case-controlled study of a Korean population. The GSTM1 and GSTT1 genotypes were determined using a polymerase chain reaction (PCR)-based method and prognostic factors, such as staging and grading were evaluated for 126 bladder cancer patients, and 204 control subjects. Smoking represented a high-risk factor (odds ratio (OR)=4.8, 95% confidence interval (CI)=2.9-8.0) for the patients with bladder cancer. The frequency of GSTM1 null individuals was higher than in the controls, but the differences were not statistically significant (OR=1.56, 95% CI=2.9-8.0). For Korean subjects who smoked more than 1 pack of cigarettes per year (PPY), the increased risk of bladder cancer was associated with the GSTM1 null genotype (OR=0.5, 95% CI=0.3-0.9). Low-stage bladder tumors were more common among the GSTM1 null genotypes (OR=2.3; 95% CI=1.1-5.5). This study suggests that in Korean subjects the GSTM1 null genotype may be associated with increased risk for bladder cancer, in a manner that appears to depend upon smoking status. And also, in bladder cancer patients the GSTM1 null genotype appears to be associated with a poorer prognosis with low stage bladder tumors.
