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At least 1,297 records · Page 72Linked to original sources
PubMed1999

Molecular mechanism of the intestinal biotin transport process.

Previous studies have characterized different aspects of the cellular/membrane mechanism and regulation of the intestinal uptake process of the water-soluble vitamin biotin. Little, however, is known about the molecular mechanisms of the uptake process. In this study, we have identified a cDNA from rat small intestine that appears to be involved in biotin transport. The open reading frame of this cloned cDNA consisted of 1,905 bases and was identical to that identified for the vitamin transporter in placental tissue. Significant heterogeneity, however, was found in the 5' untranslated region of this clone, with three distinct variants (II, III, IV) being identified in the small intestine; the placental variant (variant I), however, was not present in the small gut. Variant II was found to be the predominant form expressed in the rat small and large intestines. Functional identity of the cloned intestinal cDNA was confirmed by stable expression in COS-7 cells, which showed a four- to fivefold increase in biotin uptake in transfected COS-7 cells compared with controls. The induced biotin uptake in transfected COS-7 cells was found to be 1) Na(+) dependent, 2) saturable as a function of concentration with an apparent K(m) of 8. 77 microM and a V(max) of 779.7 pmol. mg protein(-1). 3 min(-1), and 3) inhibited by unlabeled biotin and pantothenic acid and their structural analogs. The distribution of complementary mRNA transcripts of the cloned cDNA along the vertical and longitudinal axes of the intestinal tract was also determined. Results of this study describe the molecular characteristics of the intestinal biotin absorption process and report the identification of a cDNA that encodes a Na(+)-dependent biotin uptake carrier that appears to exist in the form of multiple variants.

5' Untranslated Regions↗
PubMed2003

Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system.

It has been well established that human intestinal and liver epithelial cells transport biotin via an Na+-dependent carrier-mediated mechanism. The sodium-dependent multivitamin transport (SMVT), a biotin transporter, is expressed in both cell types. However, the relative contribution of SMVT toward total carrier-mediated uptake of physiological (nanomolar) concentrations of biotin by these cells is not clear. Addressing this issue is important, especially in light of the recent identification of a second human high-affinity biotin uptake mechanism that operates at the nanomolar range. Hence, we employed a physiological approach of characterizing biotin uptake by human-derived intestinal Caco-2 and HepG2 cells at the nanomolar concentration range. We also employed a molecular biology approach of selectively silencing the endogenous SMVT of these cells with specific small interfering RNAs (siRNAs), then examining carrier-mediated biotin uptake. The results showed that in both Caco-2 and HepG2 cells, the initial rate of biotin uptake as a function of concentration over the range of 0.1 to 50 nM to be linear. Furthermore, we found that the addition of 100 nM unlabeled biotin, desthiobiotin, or pantothenic acid to the incubation medium had no effect on the uptake of 2.6 nM [3H]biotin. Pretreatment of Caco-2 and HepG2 cells with SMVT specific siRNAs substantially reduced SMVT mRNA and protein levels. In addition, carrier-mediated [3H]biotin (2.6 nM) uptake by Caco-2 and HepG2 cells was severely (P 0.01) inhibited by the siRNAs pretreatment. These results demonstrate that the recently described human high-affinity biotin uptake system is not functional in intestinal and liver epithelial cells. In addition, the results provide strong evidence that SMVT is the major (if not the only) biotin uptake system that operates in these cells.

Amino Acid Sequence↗
PubMed2004

Biotin uptake by human proximal tubular epithelial cells: cellular and molecular aspects.

Cellular and molecular regulation of renal biotin uptake in humans is not well defined. The contribution of the human Na(+)-dependent multivitamin transporter (hSMVT) to carrier-mediated biotin uptake by human proximal tubular epithelial cells is not clear. The aim of this study was to address these issues, with the human-derived proximal tubular epithelial HK-2 cells used as a model. First, we characterized the mechanism of biotin uptake by these cells and obtained evidence for involvement of an Na(+)-, temperature-, and energy-dependent carrier-mediated uptake system. This system was inhibited by the biotin structural analog desthiobiotin, pantothenic acid, and lipoate. These findings suggest involvement of the hSMVT system in the uptake process. This was confirmed by demonstrating that the hSMVT system is expressed in HK-2 cells at the protein and mRNA levels and by selective silencing of the hSMVT gene with the use of gene-specific small interfering RNAs, which led to specific and significant inhibition of carrier-mediated biotin uptake. Of the two recently cloned promoters of the hSMVT gene, promoter 1 was more active than promoter 2 in these cells. Pretreatment of HK-2 cells with modulators of PKC- and Ca(2+)/calmodulin-mediated pathways (but not those that modulate PKA-, protein tyrosine kinase-, or nitric oxide-mediated pathways) led to significant alterations in biotin uptake. Maintaining the HK-2 cells in a biotin-deficient growth medium led to a marked upregulation in biotin transport, which was associated with an increase in hSMVT protein and RNA levels and an increase in activity of the hSMVT promoters. These results demonstrate that biotin uptake by human renal epithelial cells occurs via the hSMVT system and that the process is regulated by intracellular PKC- and Ca(2+)/calmodulin-mediated pathways. The uptake process appears to be adaptively regulated by extracellular biotin level, which involves transcriptional regulatory mechanism(s).

2,4-Dinitrophenol↗
PubMed2004

Vanin-1(-/-) mice show decreased NSAID- and Schistosoma-induced intestinal inflammation associated with higher glutathione stores.

Vanin-1 is a membrane-anchored pantetheinase highly expressed in the gut and liver. It hydrolyzes pantetheine to pantothenic acid (vitamin B5) and the low-molecular-weight thiol cysteamine. The latter is believed to be a key regulating factor of several essential metabolic pathways, acting through sulfhydryl-disulfide exchange reactions between sulfhydryl groups of the enzymes and the oxidized form, cystamine. Its physiological importance remains to be elucidated, however. To explore this point, we developed Vanin-1-deficient mice that lack free cysteamine. We examined the susceptibility of deficient mice to intestinal inflammation, either acute (NSAID administration) or chronic (Schistosoma infection). We found that Vanin-1(-/-) mice better controlled inflammatory reaction and intestinal injury in both experiments. This protection was associated with increased gamma-glutamylcysteine synthetase activity and increased stores of reduced glutathione, as well as reduced inflammatory cell activation in inflamed tissues. Oral administration of cystamine reversed all aspects of the deficient phenotype. These findings suggest that one cysteamine function is to upregulate inflammation. Consequently, the pantetheinase activity of Vanin-1 molecule could be a target for a new anti-inflammatory strategy.

Amidohydrolases↗
PubMed2006

Comparison of the effects of di(2-ethylhexyl)phthalate, a peroxisome proliferator, on the vitamin metabolism involved in the energy formation in rats fed with a casein or gluten diet.

In order to find an alleviation method for the adverse effect of environmental endocrine disrupters, we studied the effects of the putative endocrine disrupter and peroxisome proliferator, di(2-ethylhexyl)phthalate (DEHP), on animal growth and vitamin metabolism. It is known that the effects of chemical compounds such as xenobiotics differ according to the dietary protein source. We compared the effects of dietary DEHP administration on rats fed with a diet containing milk casein or wheat gluten. The increased conversion ratio of tryptophan to nicotinamide by DEHP administration was significantly higher in the casein group than in the gluten group. We also investigated the effects of DEHP on the urinary excretion of other vitamins. DEHP administration resulted in decreased urinary excretion of vitamin B(1), vitamin B(2), and pantothenic acid.

Animal Feed↗
PubMed1984

Vitamin therapy in the absence of obvious deficiency. What is the evidence?

Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking.

Acne Vulgaris↗
PubMed1984

Effect of several dermatitis preventing agents on foot pad dermatitis in dwarf and normal sized single comb white Leghorn layers.

Studies were conducted to determine the effects of increased dietary levels of vitamin and trace mineral mixtures, methionine, meat and bone meal, fish meal, and safflower oil on foot pad dermatitis in dwarf and normal size Single Comb White Leghorn layers. All layers were maintained in individual wire cages throughout a 40-week experiment period. Individual birds were scored for the incidence of foot pad dermatitis and production parameters were recorded. No significant decrease in the incidence of dermatitis was observed from the following dietary supplements: a 50% increase in a vitamin or a complete trace mineral mixture; a 50% increase in an iron, copper, iodine, and cobalt or a manganese and zinc mixture; .05% methionine; 5% meat and bone meal; 3% herring fish meal; or 2% safflower oil. It was concluded that these mixtures or supplements containing such dermatitis preventative agents as pantothenic acid, zinc, and linoleic acid appeared without effect in minimizing expression of the condition in dwarfs.

Animals↗