Hypoxia inhibits colonic uptake of the microbiota-generated forms of vitamin B1 via HIF-1α-mediated transcriptional regulation of their transporters
| العنوان: | Hypoxia inhibits colonic uptake of the microbiota-generated forms of vitamin B1 via HIF-1α-mediated transcriptional regulation of their transporters |
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| المؤلفون: | Sabui, Subrata, Ramamoorthy, Kalidas, Romero, Jose M, Simoes, Rita D, Fleckenstein, James M, Said, Hamid M |
| المصدر: | The Journal of Biological Chemistry The Journal of biological chemistry, vol 298, iss 2 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Biochemistry & Molecular Biology, 1.1 Normal biological development and functioning, HRE, hypoxia-responsive element, NF-1, neurofibromatosis-1, HIF-1α, TPP, thiamin pyrophosphate, alpha Subunit, Medical and Health Sciences, Biochemistry, THTR-1, thiamin transporter-1, human differentiated colonoid monolayers, Underpinning research, Genetics, Humans, LDHA, lactate dehydrogenase A, Thiamine, CREB, cAMP responsive element–binding protein, Hypoxia, Molecular Biology, Nutrition, Elf-3, E74-like ETS transcription factor 3, GKLF-4, gut-enriched Krüppel-like factor 4, IBD, inflammatory bowel disease, hypoxia, Microbiota, Membrane Transport Proteins, Biological Transport, THTR-2, thiamin transporter-2, Cell Biology, Biological Sciences, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, HIF, hypoxia-inducible transcription factor, PGK-1, phosphoglycerate kinase 1, Chemical Sciences, vitamin B1 uptake, cTPPT, colonic TPP transporter, DFO, desferrioxamine, Hypoxia-Inducible Factor 1, Thiamine Pyrophosphate, qPCR, quantitative PCR, SP-1, specificity protein 1, Research Article |
| الوصف: | Hypoxia exerts profound effects on cell physiology, but its effect on colonic uptake of the microbiota-generated forms of vitamin B1 (i.e., thiamin pyrophosphate [TPP] and free thiamine) has not been described. Here, we used human colonic epithelial NCM460cells and human differentiated colonoid monolayers as invitro and exvivo models, respectively, and were subjected to either chamber (1% O2, 5% CO2, and 94% N2) or chemically (desferrioxamine; 250μM)-induced hypoxia followed by determination of different physiological-molecular parameters. We showed that hypoxia causes significant inhibition in TPP and free thiamin uptake by colonic NCM460cells and colonoid monolayers; it also caused a significant reduction in the expression of TPP (SLC44A4) and free thiamin (SLC19A2 and SLC19A3) transporters and in activity of their gene promoters. Furthermore, hypoxia caused a significant induction in levels of hypoxia-inducible transcription factor (HIF)-1α but not HIF-2α. Knocking down HIF-1α using gene-specific siRNAs in NCM460cells maintained under hypoxic conditions, on the other hand, led to a significant reversal in the inhibitory effect of hypoxia on TPP and free thiamin uptake as well as on the expression of their transporters. Finally, a marked reduction in level of expression of the nuclear factors cAMP responsive element-binding protein 1 and gut-enriched Krüppel-like factor 4 (required for activity of SLC44A4 and SLC19A2 promoters, respectively) was observedunder hypoxic conditions. In summary, hypoxia causes severe inhibition in colonic TPP and free thiamin uptake that is mediated at least in part via HIF-1α-mediated transcriptional mechanisms affecting their respective transporters. |
| وصف الملف: | application/pdf |
| تدمد: | 1083-351X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97ff343a85a7aede113b010d241e7a88 https://pubmed.ncbi.nlm.nih.gov/34998824 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....97ff343a85a7aede113b010d241e7a88 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X |
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