Riboflavin Depletion Impairs Cell Proliferation in Adult Human Duodenum: Identification of Potential Effectors

Nakano, Emi; Mushtaq, Sohail; Heath, Paul R.; Lee, Eun-Sook; Bury, Jonathan; Riley, Stuart; Powers, Hilary J.; Corfe, Bernard M.

doi:10.1007/s10620-010-1374-3

Cited by 40 publications

(23 citation statements)

References 34 publications

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“…The wide spectrum of existence, function and localization of all these FAD dependent enzymes, raises the problem of their biogenesis route and dependence on FAD availability in each organelle. Given this multiplicity of cellular functions, it is not surprising that inadequate riboflavin availability, as well as derangements in FAD homeostasis, may be causative of cell degeneration and cancer (Powers 2003;Nakano et al 2011;P o w e r se ta l2011), as well as severe metabolic defects some of which are treatable with high doses of the vitamin (Gregersen 1985;G i a n a z z ae ta l2006;B a r i l e et al 2013).…”

Section: Communicated By: Manuel Schiffmentioning

confidence: 99%

Riboflavin transport and metabolism in humans

Barile

Leone

Galluccio

et al. 2016

J of Inher Metab Disea

136

143

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Recent studies elucidated how riboflavin transporters and FAD forming enzymes work in humans and create a coordinated flavin network ensuring the maintenance of cellular flavoproteome. Alteration of this network may be causative of severe metabolic disorders such as multiple acyl-CoA dehydrogenase deficiency (MADD) or Brown-Vialetto-van Laere syndrome. A crucial step in the maintenance of FAD homeostasis is riboflavin uptake by plasma and mitochondrial membranes. Therefore, studies on recently identified human plasma membrane riboflavin transporters are presented, together with those in which still unidentified mitochondrial riboflavin transporter(s) have been described. A main goal of future research is to fill the gaps still existing as for some transcriptional, functional and structural details of human FAD synthases (FADS) encoded by FLAD1 gene, a novel "redox sensing" enzyme. In the frame of the hypothesis that FADS, acting as a "FAD chaperone", could play a crucial role in the biogenesis of mitochondrial flavo-proteome, several basic functional aspects of flavin cofactor delivery to cognate apo-flavoenzyme are also briefly dealt with. The establishment of model organisms performing altered FAD homeostasis will improve the molecular description of human pathologies. The molecular and functional studies of transporters and enzymes herereported, provide guidelines for improving therapies which may have beneficial effects on the altered metabolism.

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Section: Communicated By: Manuel Schiffmentioning

confidence: 99%

Riboflavin transport and metabolism in humans

Barile

Leone

Galluccio

et al. 2016

J of Inher Metab Disea

136

143

View full text Add to dashboard Cite

show abstract

“…A role for RF in protein folding in the endoplasmic reticulum has also been identified [ 2 ]. More recent studies have identified anti-oxidant [ 3 – 5 ] and anti-inflammatory [ 6 ] properties for RF as well as a role in normal immune function [ 7 , 8 ], and in the maintenance of normal intestinal homeostasis [ 9 ]. Thus, disturbance in normal RF homeostasis is expected to lead to negative health consequences, which include degenerative changes in the nervous system, anemia, cataract and growth retardation [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Mediating the Adaptive Regulation of Intestinal Riboflavin Uptake Process

et al. 2015

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The intestinal absorption process of vitamin B2 (riboflavin, RF) is carrier-mediated, and all three known human RF transporters, i.e., hRFVT-1, -2, and -3 (products of the SLC52A1, 2 & 3 genes, respectively) are expressed in the gut. We have previously shown that the intestinal RF uptake process is adaptively regulated by substrate level, but little is known about the molecular mechanism(s) involved. Using human intestinal epithelial NCM460 cells maintained under RF deficient and over-supplemented (OS) conditions, we now show that the induction in RF uptake in RF deficiency is associated with an increase in expression of the hRFVT-2 & -3 (but not hRFVT-1) at the protein and mRNA levels. Focusing on hRFVT-3, the predominant transporter in the intestine, we also observed an increase in the level of expression of its hnRNA and activity of its promoter in the RF deficiency state. An increase in the level of expression of the nuclear factor Sp1 (which is important for activity of the SLC52A3 promoter) was observed in RF deficiency, while mutating the Sp1/GC site in the SLC52A3 promoter drastically decreased the level of induction in SLC52A3 promoter activity in RF deficiency. We also observed specific epigenetic changes in the SLC52A3 promoter in RF deficiency. Finally, an increase in hRFVT-3 protein expression at the cell surface was observed in RF deficiency. Results of these investigations show, for the first time, that transcriptional and post-transcriptional mechanisms are involved in the adaptive regulation of intestinal RF uptake by the prevailing substrate level.

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“…More specifically, Nakano and co‐workers found that duodenal biopsies from riboflavin‐deficient human subjects had shallower crypt depths and less Ki67 + cells; they further showed that in intestinal Caco‐2 cells, depletion of riboflavin altered the expression of cell cycle genes, which lead to cell cycle arrest at G2‐mitosis transition. [ 157 ] In another study on HCT116, LS174T, and SW480 cell lines, folate was demonstrated to increase both cell proliferation and genomic DNA methylation level. [ 158 ] Additionally, vitamin K2 was reported to promote absorptive lineage differentiation, and reduce EGF‐induced proliferation in Caco‐2 cells.…”

Section: Gut Microbial Metabolites and Intestinal Stem Cell Activitiesmentioning

confidence: 99%

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

2020

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Microorganisms that colonize the gastrointestinal tract, collectively known as the gut microbiota, are known to produce small molecules and metabolites that significantly contribute to host intestinal development, functions, and homeostasis. Emerging insights from microbiome research reveal that gut microbiota‐derived signals and molecules influence another key player maintaining intestinal homeostasis—the intestinal stem cell niche, which regulates epithelial self‐renewal. In this review, the literature on gut microbiota‐host crosstalk is surveyed, highlighting the effects of gut microbial metabolites on intestinal stem cells. The production of various classes of metabolites, their actions on intestinal stem cells are discussed and, finally, how the production and function of metabolites are modulated by aging and dietary intake is commented upon.

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Riboflavin Depletion Impairs Cell Proliferation in Adult Human Duodenum: Identification of Potential Effectors

Abstract: Riboflavin depletion in adult humans impairs proliferation and proliferative potential of intestinal cells, which may have implications for gastrointestinal function.

Cited by 40 publications

References 34 publications

Riboflavin transport and metabolism in humans

Riboflavin transport and metabolism in humans

Molecular Mechanisms Mediating the Adaptive Regulation of Intestinal Riboflavin Uptake Process

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

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