Chronic alcohol consumption and intestinal thiamin absorption: effects on physiological and molecular parameters of the uptake process

Thiamin is essential for normal cellular functions, and its deficiency leads to a variety of clinical abnormalities. Humans and other mammals obtain the vitamin via intestinal absorption. The intestine is exposed to two sources of thiamin, a dietary and a bacterial (i.e., normal microflora of the large intestine) source. Chronic alcohol consumption is associated with thiamin deficiency, which is caused (in part) by inhibition in intestinal thiamin absorption. However, little is known about the physiological and molecular aspects of the intestinal thiamin uptake process that are affected by chronic alcohol use. To address these issues, we used rats fed an alcohol-liquid diet and human intestinal epithelial HuTu-80 cells chronically exposed to ethanol as model systems. The results showed that chronic alcohol feeding to rats led to a significant inhibition in carrier-mediated thiamin transport across both the jejunal brush-border membrane and basolateral membrane domains. This was associated with a significant reduction in level of expression of thiamin transporter-1 (THTR-1), but not THTR-2, at the protein and mRNA levels. Level of expression of the heterogenous nuclear RNA of THTR-1 in the intestine of alcohol-fed rats was also decreased compared with their pair-fed controls. Chronic alcohol feeding also caused a significant inhibition in carrier-mediated thiamin uptake in rat colon. Studies with HuTu-80 cells chronically exposed to ethanol also showed a significant inhibition in carrier-mediated thiamin uptake. This inhibition was associated with a reduction in level of expression of human THTR-1 and THTR-2 at the protein, mRNA, and transcriptional (promoter activity) levels. These studies demonstrate that chronic alcohol feeding inhibits intestinal thiamin absorption via inhibition of the individual membrane transport event across the polarized absorptive epithelial cells. Furthermore, the inhibition is, at least in part, mediated via transcriptional mechanism(s).

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Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00465.2010 ◽

2011 ◽

Vol 300 (3) ◽

pp. G494-G501 ◽

Cited By ~ 19

Author(s):

Sandeep B. Subramanya ◽

Veedamali S. Subramanian ◽

Jeyan S. Kumar ◽

Robert Hoiness ◽

Hamid M. Said

Keyword(s):

Alcohol Use ◽

Transgenic Mice ◽

Animal Studies ◽

Molecular Mechanisms ◽

Basolateral Membrane ◽

Regulatory Region ◽

Significant Inhibition ◽

Water Soluble ◽

Rat Colon ◽

Chronic Alcohol

The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5′-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5′-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. 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.

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Chronic Alcohol Consumption Induces Genomic but Not p53-Specific DNA Hypomethylation in Rat Colon

Journal of Nutrition ◽

10.1093/jn/129.11.1945 ◽

1999 ◽

Vol 129 (11) ◽

pp. 1945-1950 ◽

Cited By ~ 88

Author(s):

Sang-Woon Choi ◽

Felix Stickel ◽

Hyun Wook Baik ◽

Young-In Kim ◽

Helmut K. Seitz ◽

...

Keyword(s):

Alcohol Consumption ◽

Rat Colon ◽

Chronic Alcohol ◽

Dna Hypomethylation ◽

Chronic Alcohol Consumption

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Chronic Alcohol Consumption and Withdrawal Do Not Induce Cell Death in the Suprachiasmatic Nucleus, But Lead to Irreversible Depression of Peptide Immunoreactivity and mRNA Levels

Journal of Neuroscience ◽

10.1523/jneurosci.17-04-01302.1997 ◽

1997 ◽

Vol 17 (4) ◽

pp. 1302-1319 ◽

Cited By ~ 74

Author(s):

M. D. Madeira ◽

J. P. Andrade ◽

A. R. Lieberman ◽

N. Sousa ◽

O. F. X. Almeida ◽

...

Keyword(s):

Cell Death ◽

Alcohol Consumption ◽

Suprachiasmatic Nucleus ◽

Mrna Levels ◽

Chronic Alcohol ◽

Chronic Alcohol Consumption ◽

Induce Cell Death

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00308.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. G896-G904 ◽

Cited By ~ 16

Author(s):

Sandeep B. Subramanya ◽

Veedamali S. Subramanian ◽

V. Thillai Sekar ◽

Hamid M. Said

Keyword(s):

Acinar Cells ◽

Normal Function ◽

Significant Inhibition ◽

Pancreatic Acinar Cells ◽

Transcriptional Level ◽

Mrna Levels ◽

Chronic Alcohol ◽

Metabolizing Enzymes ◽

Uptake Process ◽

First Time

Thiamin is important for normal function of pancreatic acinar cells, but little is known about its mechanism of uptake and about the effect of chronic alcohol use on the process. We addressed these issues using freshly isolated rat primary and rat-derived cultured AR42J pancreatic acinar cells as models. Results showed thiamin uptake by both primary and cultured AR42J pancreatic acinar cells to be via a specific carrier-mediated mechanism and that both of the thiamin transporters 1 and 2 (THTR-1 and THTR-2) are expressed in these cells. Chronic alcohol feeding of rats was found to lead to a significant inhibition of carrier-mediated thiamin uptake by pancreatic acinar cells and was associated with a significant reduction in level of expression of THTR-1 and THTR-2 at the protein and mRNA levels. Chronic exposure (96 h) of AR42J cells to alcohol also led to a significant decreased carrier-mediated thiamin uptake, an effect that was associated with a significant decrease in the activity of the human SLC19A2 and SLC19A3 promoters expressed in these cells. We also examined the effect of chronic alcohol feeding of rats on level of expression of key thiamin metabolizing enzymes (thiamin phosphokinase and thiamin pyrophosphatase) as well as on level of expression of the mitochondrial thiamin pyrophosphate transporter of pancreatic acinar cells and observed a significant inhibition in all these parameters. These results demonstrate for the first time that thiamin uptake by pancreatic acinar cells is via a carrier-mediated process and that both the THTR-1 as well as THTR-2 are expressed in these cells. Also, chronic alcohol feeding/exposure inhibits thiamin uptake process and the inhibition is, at least in part, being exerted at the transcriptional level. Furthermore, chronic alcohol feeding also negatively impacts intracellular parameters of thiamin metabolism in pancreatic acinar cells.

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