Folate malabsorption is associated with down-regulation of folate transporter expression and function at colon basolateral membrane in rats

Molecular Nutrition Food Res

Rahat

et al. 2015

Self Cite

Section: Discussionsupporting

confidence: 86%

“…Previous studies conducted on rats in various tissues have also shown decrease in folate transport on chronic alcoholism [9,10,17,18,31]. Similar results have also been observed in case of thiamine and biotin transporters [46,49].…”

Section: Discussionsupporting

confidence: 81%

Reduced SP1‐mediated transcriptional activation decreases expression of intestinal folate transporters in response to ethanol exposure

Molecular Nutrition Food Res

Rahat

et al. 2015

Self Cite

“…Consumption of high amount of alcohol can lead to mal-absorption of folate [10,11] across intestine and thus creating FD in the body [12,13]. Various in vitro and in vivo models of alcoholism have suggested that alcoholism results in alteration of folate transport and expression of folate transporters in organs like intestine, colon, kidney, liver, and pancreas too [14][15][16][17][18]. Besides alcoholism, dietary folate alterations also have been found to affect folate uptake in intestine and kidney [19,20].…”

Section: Introductionmentioning

confidence: 99%

Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency

Rahat

et al. 2015

Mol Cell Biochem

Self Cite

Excessive alcohol consumption and dietary folate inadequacy are the main contributors leading to folate deficiency (FD). The present study was planned to study regulation of folate transport in conditions of FD and ethanol exposure in human embryonic kidney cell line. Also, the reversible nature of effects mediated by ethanol exposure and FD was determined by folate repletion and ethanol removal. For ethanol treatment, HEK293 cells were grown in medium containing 100 mM ethanol, and after treatment, one group of cells was shifted on medium that was free from ethanol. For FD treatment, cells were grown in folate-deficient medium followed by shifting of one group of cells on folate containing medium. FD as well as ethanol exposure resulted in an increase in folate uptake which was due to an increase in expression of folate transporters, i.e., reduced folate carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA and protein level. The effects mediated by ethanol exposure and FD were reversible on removal of treatment. Promoter region methylation of folate transporters remained unaffected after FD and ethanol exposure. As far as transcription rate of folate transporters is concerned, an increase in rate of synthesis was observed in both ethanol exposure and FD conditions. Additionally, mRNA life of folate transporters was observed to be reduced by FD. An increased expression of folate transporters under ethanol exposure and FD conditions can be attributed to enhanced rate of synthesis of folate transporters.

“…The reduction in folate transport in these tissues was due to downregulation in the expression of folate transporters [11][12][13][14]. The reduction in folate transport in these tissues was due to downregulation in the expression of folate transporters [11][12][13][14].…”

Section: Introductionmentioning

confidence: 98%

“…Previous studies conducted in our lab have shown alteration in folate transport across absorptive surfaces of intestine, liver, pancreas, colon, and kidney in alcoholism. The reduction in folate transport in these tissues was due to downregulation in the expression of folate transporters [11][12][13][14]. On the other side, dietary folate deficiency in rats as well as in cell line is known to upregulate the transport as well as expression of folate transporters [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Regulation at multiple levels control the expression of folate transporters in liver cells in conditions of ethanol exposure and folate deficiency

Kaur

2015

BioFactors

Self Cite

Complex regulatory mechanisms control the expression of folate transporters within cells. Liver is the primary reserve of the folate stores within the body. As excessive alcohol consumption or inefficient dietary folate intake are known to create folate deficiency, so therefore the current study was designed to explore various regulatory mechanisms controlling the expression of folate transport in liver cells in conditions of ethanol exposure and folate deficiency. In order to see whether the effects mediated by the treatments are reversible or not, ethanol removal, and folate repletion was done after ethanol exposure and folate deficiency treatment respectively. Folate deficiency resulted an increase, whereas ethanol treatment decreased the folic acid uptake within the cells. The alterations in folic acid uptake were in agreement with the observed changes in the expression of folate transporters. Ethanol exposure resulted an increase in promoter methylation of reduced folate carrier; however, folate deficiency had no effect. The effects produced by ethanol exposure and folate deficiency were found to be reversible in nature as depicted in case of ethanol removal and folate repletion group. Rate of synthesis of folate transporters was found to be increased whereas half lives of mRNA of folate transporters was found to be decreased on folate deficiency treatment and reverse was the case on ethanol treatment. Overall, alteration in the expression of folate transporters under ethanol exposure and folate deficient conditions can be attributed to those regulatory mechanisms which work at the mRNA level.