HAMID SAID

..These findings show, for the first time, that the intestinal RF uptake process undergoes differentiation-dependent upregulation and suggest that this is mediated (at least in part) via transcriptional mechanisms...

..These studies also provide evidence for a casual association between SMVT function and normal intestinal health...

..Furthermore, the process appears to be regulated by extracellular and intracellular factors...

..The results also suggest that the bacterially synthesized TPP in the large intestine is bioavailable and may contribute to overall body homeostasis of vitamin B1 and, especially, to the cellular nutrition of the local colonocytes...

..These findings demonstrate, for the first time, that both mTHTR-1 and mTHTR-2 are involved in carrier-mediated thiamin uptake by pancreatic acinar cells...

..A knockout mutation of the gene, folt-1(ok1460), was shown to cause sterility, and here we investigate the source of the sterility and the effect of the folt-1 knockout on somatic function...

..In addition, results show that this transporter plays a significant role in carrier-mediated thiamin uptake in human intestine...

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..These results show, for the first time, the existence of a specific and regulated membrane carrier-mediated system for nicotinic acid transport in human liver cells...

..Furthermore, clinical mutants of THTR-1 impair thiamin uptake via different mechanisms...

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..Intracellular trafficking of the hSMVT protein appears to involve distinct trafficking vesicles that require an intact microtubules network and the motor protein dynein for their mobility...

..Such expansion of knowledge has also covered the field of intestinal absorption of water-soluble vitamins and is the subject of this review...

..This system is pH dependent and amiloride sensitive and appears to be under the regulation of an intracellular PKA-mediated pathway...

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..This mechanism appears to be regulated by extracellular vitamin B(6) levels and an intracellular Ca(2+)/calmodulin-mediated pathway...

..It is suggested that bacterially synthesized thiamine in the large intestine may contribute to thiamine nutrition of the host, especially toward cellular nutrition of the local colonocytes...

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..Furthermore, the upregulation in folate uptake is associated with an increase in mRNA and protein levels of folate carrier, suggesting possible involvement of a transcriptional regulatory mechanism(s) in the upregulation...

..In addition, SLC19A2 was found to be the predominant thiamin uptake carrier expressed in these cells and its promoter displays a high level of activity in them...

..It is suggested that the identified transport system may be involved in the absorption of bacterially synthesized RF in the large intestine and that this source of RF may contribute toward RF homeostasis, especially that of colonocytes...

..Furthermore, the uptake process seems to be regulated by an intracellular Ca2+/calmodulin-mediated pathway and by extracellular substrate levels...

..2000; Said and Seetheram 2006), and thus, for more information the reader is advised to consider these additional sources...

..In addition, chronic alcohol feeding leads to a marked inhibition in folate uptake by pancreatic acinar cells, an effect that is associated with reduction in level of expression of RFC and PCFT...

..Furthermore, chronic alcohol feeding also negatively impacts intracellular parameters of thiamin metabolism in pancreatic acinar cells...

..These studies demonstrate for the first time that Tspan-1 is an interacting partner with hTHTR-1 and that this interaction affects hTHTR-1 stability...

..These findings demonstrate for the first time that chronic ethanol feeding inhibits renal biotin transport and that this effect is, at least in part, being exerted at the transcriptional level...

..These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding...

..Our results show important role for His¹¹⁵ and His²⁵⁴ residues in hSMVT function, which is most probably mediated via an effect on level of hSMVT expression at the cell membrane...

..Further, clinically relevant mutations in hTHTR-1 lead to impaired cell surface expression or function of the transporter in retinal epithelial ARPE-19 cells...

..Finally, we compared the behavior of hTHTR2 with that of hTHTR1 and the human reduced folate carrier (SLC19A1) to underscore commonalities in the cell surface targeting mechanisms of the entire SLC19A gene family...

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..For the first time, these data define the mechanisms that control the intracellular trafficking and cell surface localization of hRFC within mammalian epithelia...

..These results cast doubt on the most parsimonious explanation for the BBGD phenotype, namely that hTHTR2 is a physiological biotin transporter...

..The uptake process appears to be adaptively regulated by extracellular biotin level, which involves transcriptional regulatory mechanism(s)...

..In contrast, the steady-state localization of occludin at the cell surface was dependent on intact microfilaments but not microtubules...

..Hence, food fortification and intake of supplemental folate are widespread...

..For the first time, our data present information regarding structure-function and membrane targeting of the hPCFT polypeptide, as well as the mechanisms that control its steady-state expression in polarized cells...

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..Third, apical targeting was lost on deletion of a helical-prone region between amino acids 570-584. We conclude that the COOH tail of hSMVT contains several determinants important for polarized targeting and biotin transport...

..Furthermore, the inhibition appears to be dependent on a functional TTSS of EPEC...

..We tested this possibility and examined the role of THTR-2 in uptake of thiamin in the intestine of mice...

..In addition, the ontogenic changes observed in the intestinal biotin uptake process involve the entry step of the vitamin at the BBM and appear to be mediated via a transcriptional mechanism(s)...

..In addition, the results provide strong evidence that SMVT is the major (if not the only) biotin uptake system that operates in these cells...

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..Our results provide the first direct resolution of functional hSVCT1 expression at the apical cell surface of polarized epithelia and define an apical targeting signal of relevance to transporters of diverse substrate specificity...

..05) decrease in folate uptake. This study demonstrates for the first time the identification of DYNLRB1 as an interacting protein partner with hRFC. Furthermore, DYNLRB1 appears to influence the function and cell biology of hRFC...

..In addition, the studies suggest the possible involvement (at least in part) of a transcriptional mechanism(s) in this type of regulation of the intestinal folate uptake process...

..Furthermore, the inhibition is, at least in part, mediated via transcriptional mechanism(s)...

..These studies demonstrate, for the first time, the functional existence of a specific and regulatable carrier-mediated process for pyridoxine uptake by mammalian colonocytes...

..These results demonstrate for the first time that folate transport across the intestinal BBM is under ontogenic regulation during early stages of life and that this regulation involves a transcriptional regulatory mechanism(s)...

..The results also show the involvement of hRFC in the uptake process and suggest the possible involvement of intracellular cAMP- and PTK-mediated pathways in the regulation of folate uptake...

..In addition, folate-deficiency was found to up-regulate folate uptake by human intestinal epithelial cells and that this regulation involves activation of hRFC pB...

..Our results reveal a spectrum of mutant phenotypes, underlining that TRMA can result from decreased thiamine transport activity underpinned by changes in hTHTR1 expression levels, cellular targeting and/or protein transport activity...

..The results also suggest the possible involvement of a PTK-mediated pathway in the regulation of niacin uptake...

..Thus C. elegans provides a genetically tractable model that can be used to study integrative aspects of the folate uptake process in the context of the whole animal level...

..These studies are the first to determine the overall ascorbic acid uptake process and relative expression, regulation, and contribution of the hSVCT systems in human liver epithelial cells...

..In addition, the results provide the first characterization of the SLC19A2 promoter. These findings raise the possibility that SLC19A2 may play a role in the normal intestinal thiamine absorption process...

..The results demonstrate, for the first time, the importance of KLF-4 and AP-2 in regulating the activity of the hSMVT promoter in the intestine and provide direct in vivo confirmation of hSMVT promoter activity...

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..N-Glycosylation is therefore essential for vitamin C transporter functionality...

..Results also show conserved TM anionic residue of the SLC19A2 protein is critical for its function. Furthermore, native SLC19A2 is glycosylated, but this is not important for its function...

..These results demonstrate the first molecular characterization of the regulatory region of this important human gene...

..These studies report the first characterization of the SLC19A3 promoter in vitro and in vivo and demonstrate the importance of an SP1 cis-regulatory element in regulating promoter activity of this important human gene...

..These results demonstrate that the RFC system is the major (if not the only) folate uptake system that is functional in intestinal epithelial cells...

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..These results demonstrate a potential role for specific cysteine residues in the cell surface expression of the hRFT2 in human intestinal epithelial cells...

..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...

..These results demonstrate for the first time that PDZD11 is an interacting partner with hSMVT in intestinal epithelial cells and that this interaction affects hSMVT function and cell biology...

..The results demonstrate the importance of GKLF, NF-1, and SP-1 in regulating the activity of the SLC19A2 promoter and provide direct in vivo confirmation of promoter activity...

..Taken together, these results correlate hTHTR1 structure with cellular expression profile and reveal a critical dependence on hTHTR1 backbone integrity and microtubule-based trafficking processes for functional expression of hTHTR1...

..38 +/- 0.35 pmol/mg protein/10 sec). These results indicate the presence of a proton gradient-dependent specialized carrier-mediated exchange mechanism for thiamine transport across the human jejunum basolateral membranes...

..The increase in permeability was associated with NF-kappa B-dependent downregulation of ZO-1 protein expression and alteration in junctional localization...

..It is uncertain whether activities of biotin-dependent pathways in placenta affect fetal development in vivo...

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..Such polarization decreases functional redundancy between transporter isoforms and allows for independent regulation of thiamine import and export pathways in cells...

..Instead, these proteins accumulated in intracellular granules, and were, apparently, degraded. Hence, it is unlikely that these minor splicing forms are directly involved in solute transport across the plasma membrane...

..abstract_text> ..

..Results of these investigations should help in the designing of effective strategies to optimize biotin body levels, especially in conditions associated with biotin deficiency and sub-optimal levels. 1 ..

..This should ultimately assist us in the design of effective strategies to optimize biotin body homeostasis in conditions associated with biotin deficiency and sub-optimal levels. ..

..This should ultimately assist us in the designing of effective strategies to optimize thiamin body homeostasis in conditions associated with thiamin deficiency and sub-optimal levels. ..

..This should be of great value in future investigations into the mechanisms and regulation of transport of water-soluble vitamins in the intestine (and other tissues) at the integrated whole animal level in vivo. ..

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..This should ultimately assist us in the design of effective strategies to optimize biotin body homeostasis in conditions associated with biotin deficiency and sub-optimal levels. ..

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..These results should also contribute toward our understanding of regulation of SMVT function in other tissues that have been shown to express this transport system. ..