Effect of chronic alcohol feeding on physiological and molecular parameters of renal thiamin transport

Abstract

Subramanian VS, Subramanya SB, Tsukamoto H, Said HM. Effect of chronic alcohol feeding on physiological and molecular parameters of renal thiamin transport. Am J Physiol Renal Physiol 299: F28-F34, 2010. First published April 28, 2010 doi:10.1152/ajprenal.00140.2010.-The renal thiamin reabsorption process plays an important role in regulating thiamin body homeostasis and involves both thiamin transporters-1 and -2 (THTR1 and THTR2). Chronic alcohol use is associated with thiamin deficiency. Although a variety of factors contribute to the development of this deficiency, effects of chronic alcohol use on renal thiamin transport have not been thoroughly examined. We addressed this issue by examining the effect of chronic alcohol feeding of rats with liquid diet on physiological and molecular parameters of renal thiamin transport. Chronic alcohol feeding caused a significant inhibition in carrier-mediated thiamin transport across the renal brushborder membrane and was evident as early as 2 wk after initiation of alcohol feeding. Similarly, thiamin transport across the renal basolateral membrane was significantly inhibited by chronic alcohol feeding. The inhibition in renal thiamin transport was associated with a marked decrease in the level of expression of THTR1 and -2 proteins, mRNAs, and heterogeneous nuclear RNAs. Chronic alcohol feeding also caused a significant reduction in the level of expression of thiamin pyrophosphokinase but not that of the mitochondrial thiamin pyrophosphate transporter. These studies show that chronic alcohol feeding inhibits the entry and exit of thiamin in the polarized renal epithelial cells and that the effect is, at least in part, mediated at the transcriptional level. These findings also suggest that chronic alcohol feeding interferes with the normal homeostasis of thiamin in renal epithelial cells.transporter; vitamin B1; kidney; thiamin transporter-1; thiamin transporter-2 THIAMIN, A WATER-SOLUBLE vitamin, is essential for cellular function, growth, and development. The vitamin is enzymatically converted into its active form, thiamin pyrophosphate (TPP), in the cytoplasm via the action of thiamin pyrophosphokinase (TPKase), a rate-limiting enzyme that plays an important role in regulating cellular thiamin homeostasis. While all mammalian nucleated cells possess the ability to convert thiamin to TPP, the liver and kidneys are especially active in this regard (10,22,36). TPP is then either used in the cytoplasm or is imported in the mitochondria via a carriermediated process that involves the mitochondrial TPP transporter (encoded by the SLC25A19 gene; see Ref. 19), for utilization in carbohydrate metabolism and energy production. The importance of thiamin for human health and well-being is evident by the range of clinical abnormalities that result from its deficiency, which include cardiovascular and neurological disorders (4, 31, 35). Beriberi and the Wernicke-Korsakoff syndrome are well-known thiamin deficiency diseases (24, 35).All mammals cannot synthesize thiamin; thus, the...

Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol feeding/exposure

“…This inhibition was associated with a significant reduction in the level of expression of the THTR-1 and THTR-2 protein and mRNA. This effect of alcohol on expression of THTR-1 and THTR-2 is similar to what we have recently observed in the kidneys (30); it is, however, in contrast to what was observed in the intestine where expression of THTR-1 but not THTR-2 was affected by chronic alcohol use (32). These findings demonstrate a differential sensitivity of thiamin transporters to chronic alcohol exposure in different tissues.…”

“…Despite the importance of thiamin for normal metabolism and function of pancreatic acinar cells, there is little known about the mechanisms involved in the vitamin uptake by these cells and about the factors or conditions that negatively affect the process. One such factor could be chronic alcohol use, which is known to be associated with systemic thiamin deficiency and with inhibition in intestinal and renal thiamin absorption and reabsorption (30,32). Chronic alcohol use has also been shown to negatively impact intracellular thiamin metabolism in a tissue-specific manner (27).…”

“…The coding region of rat THTR-1, THTR-2, TPKase, TPPase, mitochondrial thiamin pyrophosphate (SLC19A25 gene), and ␤-actin, were PCR amplified by use of gene-specific primers (Table 1) for real-time PCR study. Real-time PCR conditions were same as described previously (30). The data were normalized to ␤-actin and then quantified by a relative relationship method supplied by the vendor (Bio-Rad) (16).…”

Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake

“…Chronic alcohol use is associated with systemic thiamin deficiency that is believed to be, at least in part, mediated via inhibition in intestinal absorption and renal reabsorption of the vitamin (23,24). Chronic alcohol use has also been shown to interfere with normal intracellular metabolism of thiamin that is tissue specific in nature (19).…”

Salmonellainfection inhibits intestinal biotin transport: cellular and molecular mechanisms

“…Because changes in the mRNA of a given gene could be mediated by changes in the transcription rate of that gene, we examined the effect of S. typhimurium infection on the expression levels of the endogenous Slc5a6 hnRNA; the level of hnRNA reflects rate of transcription (13,47). We found a significant (P Ͻ 0.01) decrease in the level of Slc5a6 hnRNA in the jejunum of the S. typhimurium-infected mice compared with controls ( Fig.…”