Molecular mechanisms involved in the adaptive regulation of the colonic thiamin pyrophosphate uptake process

Anandam, K; Srinivasan, Padmanabhan; Subramanian, Veedamali S.; Said, Hamid M.

doi:10.1152/ajpcell.00169.2017

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…In another study, we examined the effect of infecting NCM460 cells with EHEC (200 MOI; 5 h exposure) on level of TPPT protein expression. This was done by means of western blotting using specific polyclonal antibodies against the TPP transporter [25]. The result showed a significant (P < 0.01) reduction in the level of expression of the TPPT protein in cells infected with EHEC compared to uninfected controls (Fig 1D).…”

Section: Resultsmentioning

confidence: 99%

“…We also shown that this uptake system is specific for TPP and does not transport the free form of vitamin B1, i. e., free thiamin. In addition, we have characterized different cell biology and regulatory aspects of this colonic TPPT system [20, 24, 25]. Currently, there is little known about the effect of external/ environmental factors on the function of this newly identified uptake system.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies from our laboratory have shown that expression of the SLC44A4 system in the gastrointestinal tract is restricted to the large intestine [21], and that this site-specific expression is determined by epigenetic mechanisms [23]. In addition, we have characterized different regulatory aspects of the TPPT system, identified a role for the cis-regulatory elements CREB-1 and ETS/ELF3 in basal activity of the SLC44A4 promoter [24], and showed that the colonic TPP uptake process is adaptively-regulated by the prevailing extracellular substrate level [20, 25]. Very little, however, is known about the effect of external factors (including that of enteric pathogens) on the colonic TPP uptake process.…”

Section: Introductionmentioning

confidence: 99%

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Enterohemorrhagic Escherichia coli infection inhibits colonic thiamin pyrophosphate uptake via transcriptional mechanism

et al. 2019

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Colonocytes possess a specific carrier-mediated uptake process for the microbiota-generated thiamin (vitamin B1) pyrophosphate (TPP) that involves the TPP transporter (TPPT; product of the SLC44A4 gene). Little is known about the effect of exogenous factors (including enteric pathogens) on the colonic TPP uptake process. Our aim in this study was to investigate the effect of Enterohemorrhagic Escherichia coli (EHEC) infection on colonic uptake of TPP. We used human-derived colonic epithelial NCM460 cells and mice in our investigation. The results showed that infecting NCM460 cells with live EHEC (but not with heat-killed EHEC, EHEC culture supernatant, or with non-pathogenic E. Coli) to lead to a significant inhibition in carrier-mediated TPP uptake, as well as in level of expression of the TPPT protein and mRNA. Similarly, infecting mice with EHEC led to a significant inhibition in colonic TPP uptake and in level of expression of TPPT protein and mRNA. The inhibitory effect of EHEC on TPP uptake by NCM460 was found to be associated with reduction in the rate of transcription of the SLC44A4 gene as indicated by the significant reduction in the activity of the SLC44A4 promoter transfected into EHEC infected cells. The latter was also associated with a marked reduction in the level of expression of the transcription factors CREB-1 and ELF3, which are known to drive the activity of the SLC44A4 promoter. Finally, blocking the ERK1/2 and NF-kB signaling pathways in NCM460 cells significantly reversed the level of EHEC inhibition in TPP uptake and TPPT expression. Collectively, these findings show, for the first time, that EHEC infection significantly inhibit colonic uptake of TPP, and that this effect appears to be exerted at the level of SLC44A4 transcription and involves the ERK1/2 and NF-kB signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enterohemorrhagic Escherichia coli infection inhibits colonic thiamin pyrophosphate uptake via transcriptional mechanism

et al. 2019

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“…Mice were euthanized, the colonic tissue was removed and prepared colonic crypts as described before [41–43]. The generated colonoids were treated with 1mM NaB for 24 hrs and used for mRFVT3 protein, mRNA and hnRNA expression studies.…”

Section: Methodsmentioning

confidence: 99%

“…For ex vivo studies, we used 8–10-weeks old male C57BL/6 mice (Jackson Laboratory, Bar Harbor, ME) to generate colonoids as described before [41–43]. Mice were euthanized, the colonic tissue was removed and prepared colonic crypts as described before [41–43]. The generated colonoids were treated with 1mM NaB for 24 hrs and used for mRFVT3 protein, mRNA and hnRNA expression studies.…”

Section: Methodsmentioning

confidence: 99%

Sodium Butyrate Enhances Intestinal Riboflavin Uptake via Induction of Expression of Riboflavin Transporter-3 (RFVT3)

et al. 2018

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Background: Uptake of riboflavin (RF) by intestinal epithelial cells occurs via a specific carrier-mediated process that involves the apically localized RF transporter-3 (RFVT3). Previous studies have shown that sodium butyrate (NaB) affects intestinal uptake of other substrates and expression of their membrane transporters, but its effect on intestinal uptake of RF and expression of RFVT3 has not been examined. Aims: To investigate the effect of NaB on intestinal RF uptake process and expression of the RFVT3. Methods: Two experimental models were used in this study: Human-derived intestinal epithelial Caco-2 cells and ex vivo mouse colonoids. 3H-RF uptake assay, western blot, RT-qPCR and chromatin immunoprecipitation (ChIP) assay were performed. Results: Treating Caco-2 cells with NaB led to a significant increase in carrier-mediated RF uptake. This increase was associated with a significant induction in the level of expression of the hRFVT3 protein, mRNA and heterogenous nuclear RNA (hnRNA) Similarly, treating mouse colonoids with NaB led to a marked increase in the level of expression of the mRFVT3 protein, mRNA and hnRNA. NaB did not affect hRFVT3 mRNA stability, rather it caused significant epigenetic changes (histone modifications) in the SLC52A3 gene where an increase in H3Ac and a reduction in H3K27me3 levels were observed in the NaB treated Caco-2 cells compared to untreated controls. Conclusion: These findings demonstrate that NaB up-regulates intestinal RF uptake and that the effect appears to be mediated, at least in part, at the level of transcription of the SLC52A3 gene and may involve epigenetic mechanism(s).

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Gastrointestinal Handling of Water‐Soluble Vitamins

Said

Nexø

2018

Comprehensive Physiology

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Molecular mechanisms involved in the adaptive regulation of the colonic thiamin pyrophosphate uptake process

Cited by 8 publications

References 40 publications

Enterohemorrhagic Escherichia coli infection inhibits colonic thiamin pyrophosphate uptake via transcriptional mechanism

Enterohemorrhagic Escherichia coli infection inhibits colonic thiamin pyrophosphate uptake via transcriptional mechanism

Sodium Butyrate Enhances Intestinal Riboflavin Uptake via Induction of Expression of Riboflavin Transporter-3 (RFVT3)

Gastrointestinal Handling of Water‐Soluble Vitamins

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