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Article ; Online: Common Genetic Variants in the Bile Acid Synthesis Enzyme CYP7A1 Are Associated With Severe Primary Bile Acid Diarrhea.

Balesaria, Sara / Pattni, Sanjeev S / Johnston, Ian M / Nolan, Jonathan D / Appleby, Richard N / Walters, Julian R F

2022 Volume 163, Issue 2, Page(s) 517–519.e2

MeSH term(s)	Bile Acids and Salts ; Cholesterol 7-alpha-Hydroxylase/metabolism ; Diarrhea/genetics ; Humans ; Lipogenesis
Chemical Substances	Bile Acids and Salts ; CYP7A1 protein, human (EC 1.14.14.23) ; Cholesterol 7-alpha-Hydroxylase (EC 1.14.14.23)
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2022.05.005
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Article ; Online: Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption.

Bayele, Henry K / Balesaria, Sara / Srai, Surjit K S

Free radical biology & medicine

2015 Volume 89, Page(s) 1192–1202

Abstract: Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and ... ...

Abstract	Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis.
MeSH term(s)	Animals ; Antioxidant Response Elements/genetics ; Blotting, Western ; Chromatin Immunoprecipitation ; Electrophoretic Mobility Shift Assay ; Flow Cytometry ; Gene Expression Regulation/drug effects ; Hepcidins/genetics ; Hepcidins/metabolism ; Humans ; Iron/metabolism ; Male ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Phytoestrogens/pharmacology ; RNA, Messenger/genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured
Chemical Substances	HAMP protein, human ; Hepcidins ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Phytoestrogens ; RNA, Messenger ; Iron (E1UOL152H7)
Language	English
Publishing date	2015-11-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2015.11.001
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Article ; Online: Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues.

Lesjak, Marija / Balesaria, Sara / Skinner, Vernon / Debnam, Edward S / Srai, Surjit Kaila S

European journal of nutrition

2018 Volume 58, Issue 2, Page(s) 743–753

Abstract: Purpose: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have ... ...

Abstract	Purpose: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metabolism. Methods: Rats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins. Results: Both oral and intraperitoneal (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake. Conclusions: Oral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anaemia, the most widespread nutritional disorder in the world.
MeSH term(s)	Animals ; Antioxidants/pharmacology ; Duodenum/drug effects ; Duodenum/metabolism ; Gene Expression/drug effects ; Intestinal Absorption/drug effects ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Iron/metabolism ; Male ; Models, Animal ; Quercetin/pharmacology ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Antioxidants ; Quercetin (9IKM0I5T1E) ; Iron (E1UOL152H7)
Language	English
Publishing date	2018-03-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1466536-0
ISSN	1436-6215 ; 1436-6207
ISSN (online)	1436-6215
ISSN	1436-6207
DOI	10.1007/s00394-018-1680-7
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Article: Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues

Lesjak, Marija / Balesaria, Sara / Skinner, Vernon / Debnam, Edward S / Srai, Surjit Kaila S

European journal of nutrition. 2019 Mar., v. 58, no. 2

2019

Abstract: PURPOSE: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have ... ...

Abstract	PURPOSE: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metabolism. METHODS: Rats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins. RESULTS: Both oral and intraperitoneal (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake. CONCLUSIONS: Oral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anaemia, the most widespread nutritional disorder in the world.
Keywords	blood serum ; genes ; hepcidin ; intestines ; iron ; iron absorption ; iron deficiency anemia ; liquid chromatography ; liver ; metabolites ; mucosa ; nutrient deficiencies ; polyphenols ; quercetin ; radiolabeling ; rats ; tandem mass spectrometry ; transferrin
Language	English
Dates of publication	2019-03
Size	p. 743-753.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	1466536-0
ISSN	1436-6215 ; 1436-6207
ISSN (online)	1436-6215
ISSN	1436-6207
DOI	10.1007/s00394-018-1680-7
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Article ; Online: Identification, cloning and characterization of a plasma membrane zinc efflux transporter, TrZnT-1, from fugu pufferfish (Takifugu rubripes).

Balesaria, Sara / Hogstrand, Christer

The Biochemical journal

2006 Volume 394, Issue Pt 2, Page(s) 485–493

Abstract: An orthologue of the mammalian ZnT-1 (zinc transporter-1) gene was cloned from the intestine of the torafugu pufferfish (Takifugu rubripes), demonstrating that this gene predates the evolution of land-living vertebrates. TrZnT-1 (T. rubripes ZnT-1) ... ...

Abstract	An orthologue of the mammalian ZnT-1 (zinc transporter-1) gene was cloned from the intestine of the torafugu pufferfish (Takifugu rubripes), demonstrating that this gene predates the evolution of land-living vertebrates. TrZnT-1 (T. rubripes ZnT-1) shares overall topology with other members of the ZnT-1 family of zinc transporters, with six TMs (transmembrane domains) including a large histidine-rich intracellular loop between TM IV and V and intracellular C- and N-termini. Expression of TrZnT-1 in a metallothionein acquiescent cell line suggested that this protein reduces intracellular Zn2+ levels. Manipulation of the transporting media showed that several externally applied hydrominerals had no effect on TrZnT-1 activity. However, addition of N-ethylmaleimide increased TrZnT-1-mediated transport, possibly by increasing intracellular free Zn2+ levels by Zn2+ release from carrier proteins. Generation of a specific antibody and subsequent immunocytochemistry on fixed cells overexpressing TrZnT-1 indicated that the protein is localized to the plasma membrane in these cells. The genomic organization of TrZnT-1 is the same as that in mammals with two exons. The upstream regulatory region of the TrZnT-1 gene contains several putative cis-acting elements, including metal-response elements and an Sp1 site. Analysis of the DNA contigs surrounding the TrZnT-1 gene reveal limited synteny between corresponding regions in the rat, mouse and human; however, this was very low, with only two syntenic genes, ZnT-1 and NEK2 (never in mitosis gene A-related kinase).
MeSH term(s)	Amino Acid Sequence ; Animals ; Carrier Proteins/chemistry ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Line ; Cell Membrane/metabolism ; Cloning, Molecular ; DNA, Complementary ; Gene Expression Regulation ; Molecular Sequence Data ; Phylogeny ; Promoter Regions, Genetic ; Sequence Alignment ; Sequence Homology, Amino Acid ; Takifugu/genetics
Chemical Substances	Carrier Proteins ; DNA, Complementary ; zinc-binding protein
Language	English
Publishing date	2006-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BJ20050627
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Article ; Online: Human duodenum responses to vitamin D metabolites of TRPV6 and other genes involved in calcium absorption.

Balesaria, Sara / Sangha, Sonia / Walters, Julian R F

American journal of physiology. Gastrointestinal and liver physiology

2009 Volume 297, Issue 6, Page(s) G1193–7

Abstract: Calcium absorption by the intestine is necessary for bone mineralization. Much has been learned about this process and the role of vitamin D metabolites in gene transcription from animal studies, but the molecular mechanisms in humans are less well ... ...

Abstract	Calcium absorption by the intestine is necessary for bone mineralization. Much has been learned about this process and the role of vitamin D metabolites in gene transcription from animal studies, but the molecular mechanisms in humans are less well understood. We have used samples of normal human duodenal mucosa, obtained at endoscopy, to investigate the effects of the vitamin D metabolites, 1alpha-dihydroxycholecalciferol [1,25(OH)(2)D(3)] and 25-hydroxycholecalciferol (25OHD), on transcripts on genes involved in calcium absorption and vitamin D metabolism. TRPV6 transcripts were significantly higher after incubation for 6 h with 1,25(OH)(2)D(3) (10(-9) mol/l) than after control incubations (median difference 3.1-fold, P < 0.001). Unexpectedly, TRPV6 expression was also higher (2.4-fold, P < 0.02) after incubation with 25OHD (10(-7) mol/l). Transcripts for the calcium-ATPase, PMCA1, were significantly higher with 1,25(OH)(2)D(3); CYP24 transcripts were reliably detected after incubation with either metabolite, but calbindin-D9k transcripts were unaffected. The response of TRPV6 to 25OHD and the expression of transcripts for CYP27B1, the 25OHD-1alpha-hydroxylase, were significantly correlated (r = 0.82, P < 0.02). Basal duodenal expression of TRPV6 and CYP27B1 were significantly associated (r = 0.72, P < 0.001) in a separate previously reported series of subjects. Multiple regression analysis of the associations with basal duodenal TRPV6 expression identified CYP27B1 expression and serum 1,25(OH)(2)D as major factors. Expression of the CYP27B1 protein was demonstrated immunohistochemically in duodenal mucosa. This study has shown that human duodenal TRPV6, PMCA1, and CYP24 transcripts respond rapidly to 1,25(OH)(2)D(3) and provides evidence suggesting that local duodenal production of 1,25(OH)(2)D(3) by 25OHD-1alpha-hydroxylase may have a role in human calcium absorption.
MeSH term(s)	25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; Adult ; Aged ; Aged, 80 and over ; Calcifediol/metabolism ; Calcitriol/metabolism ; Calcium/metabolism ; Calcium Channels/genetics ; Duodenoscopy ; Duodenum/enzymology ; Duodenum/metabolism ; Humans ; Intestinal Absorption/genetics ; Intestinal Mucosa/enzymology ; Intestinal Mucosa/metabolism ; Middle Aged ; Organ Culture Techniques ; Plasma Membrane Calcium-Transporting ATPases/genetics ; RNA, Messenger/metabolism ; Steroid Hydroxylases/genetics ; TRPV Cation Channels/genetics ; Up-Regulation ; Vitamin D3 24-Hydroxylase ; Young Adult
Chemical Substances	ATP2B1 protein, human ; Calcium Channels ; RNA, Messenger ; TRPV Cation Channels ; TRPV6 protein, human ; Steroid Hydroxylases (EC 1.14.-) ; Vitamin D3 24-Hydroxylase (EC 1.14.15.16) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.15.18) ; Plasma Membrane Calcium-Transporting ATPases (EC 3.6.3.8) ; Calcitriol (FXC9231JVH) ; Calcifediol (P6YZ13C99Q) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2009-09-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00237.2009
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Article ; Online: Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.

Lesjak, Marija / Hoque, Rukshana / Balesaria, Sara / Skinner, Vernon / Debnam, Edward S / Srai, Surjit K S / Sharp, Paul A

PloS one

2014 Volume 9, Issue 7, Page(s) e102900

Abstract: Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it ... ...

Abstract	Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin--the most abundant dietary polyphenol--are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.
MeSH term(s)	3' Untranslated Regions ; Animals ; Caco-2 Cells ; Cation Transport Proteins/antagonists & inhibitors ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Duodenum/drug effects ; Duodenum/metabolism ; Gene Expression/drug effects ; Homeostasis/physiology ; Humans ; Intestinal Absorption/drug effects ; Intestinal Absorption/physiology ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Ion Transport/drug effects ; Iron Chelating Agents/pharmacology ; Iron, Dietary/metabolism ; Male ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Quercetin/pharmacology ; Rats ; Rats, Sprague-Dawley
Chemical Substances	3' Untranslated Regions ; Cation Transport Proteins ; Iron Chelating Agents ; Iron, Dietary ; MicroRNAs ; metal transporting protein 1 ; Quercetin (9IKM0I5T1E)
Language	English
Publishing date	2014-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0102900
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Article ; Online: Divalent metal-dependent regulation of hepcidin expression by MTF-1.

Balesaria, Sara / Ramesh, Bala / McArdle, Harry / Bayele, Henry K / Srai, Surjit K S

FEBS letters

2009 Volume 584, Issue 4, Page(s) 719–725

Abstract: Hepcidin is a small acute phase peptide that regulates iron absorption. It is induced by inflammation and infection, but is repressed by anaemia and hypoxia. Here we further reveal that hepcidin transcription also involves interactions between functional ...

Abstract	Hepcidin is a small acute phase peptide that regulates iron absorption. It is induced by inflammation and infection, but is repressed by anaemia and hypoxia. Here we further reveal that hepcidin transcription also involves interactions between functional metal response elements (MREs) in its promoter, and the MRE-binding transcription factor-1. Analysis of hepcidin mRNA and protein levels in hepatoma cells suggests that its expression may be regulated by divalent metal ions, with zinc inducing maximal effects on hepcidin levels. These data suggest that this peptide may be a pleiotropic sensor of divalent metals, some of which are xenobiotic environmental toxins.
MeSH term(s)	Antimicrobial Cationic Peptides/genetics ; Antimicrobial Cationic Peptides/metabolism ; Binding Sites/genetics ; Blotting, Western ; Cations, Divalent/pharmacology ; Cell Line, Tumor ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation/drug effects ; Hepcidins ; Humans ; Luciferases/genetics ; Luciferases/metabolism ; Metals/pharmacology ; Mutation ; Promoter Regions, Genetic/genetics ; Protein Binding ; Response Elements/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; Transfection ; Zinc/pharmacology ; Transcription Factor MTF-1
Chemical Substances	Antimicrobial Cationic Peptides ; Cations, Divalent ; DNA-Binding Proteins ; HAMP protein, human ; Hepcidins ; Metals ; Transcription Factors ; Luciferases (EC 1.13.12.-) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2009-12-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1016/j.febslet.2009.12.023
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Article: Application of genomics and proteomics for study of the integrated response to zinc exposure in a non-model fish species, the rainbow trout.

Hogstrand, Christer / Balesaria, Sara / Glover, Chris N

Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology

2002 Volume 133, Issue 4, Page(s) 523–535

Abstract: The advent of DNA array technology and proteomics has revolutionised biology by allowing global analysis of cellular events. So far, the benefits from these new techniques have primarily been realised for well-characterised species. These organisms are ... ...

Abstract	The advent of DNA array technology and proteomics has revolutionised biology by allowing global analysis of cellular events. So far, the benefits from these new techniques have primarily been realised for well-characterised species. These organisms are rarely the most relevant for environmental biology and ecotoxicology. Thus, there is a need to explore new ways to exploit transcriptomics and proteomics for non-model species. In the present study, rainbow trout (Oncorhynchus mykiss) were exposed to a sublethal concentration of waterborne zinc for up to 6 days. The response in gill tissue was investigated by differential screening of a heterologous cDNA array and by protein profiling using Surface Enhanced Laser Desorption/Ionisation (SELDI). The cDNA array, which was a high-density spotted library of cDNA from Fugu rubripes gill, revealed differentially expressed genes related to energy production, protein synthesis, paracellular integrity, and inflammatory response. SELDI analysis yielded seven proteins that were consistently present only in zinc-exposed gills, and four proteins unique to gills from control fish. A further 11 proteins were differentially regulated. Identification of these proteins by bioinformatics proved difficult in spite of detailed information on molecular mass, charge and zinc-binding affinity. It is concluded that these approaches are viable to non-model species although both have clear limitations.
MeSH term(s)	Animals ; Biomarkers/analysis ; Environmental Exposure ; Gene Expression Profiling ; Gene Expression Regulation ; Genomics ; Gills/drug effects ; Mass Spectrometry/instrumentation ; Mass Spectrometry/methods ; Oligonucleotide Array Sequence Analysis ; Oncorhynchus mykiss/genetics ; Oncorhynchus mykiss/metabolism ; Protein Array Analysis ; Proteomics ; Zinc/toxicity
Chemical Substances	Biomarkers ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2002-11-25
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	121247-3
ISSN	1879-1107 ; 1096-4959 ; 0305-0491
ISSN (online)	1879-1107
ISSN	1096-4959 ; 0305-0491
DOI	10.1016/s1096-4959(02)00125-2
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Article ; Online: Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.

Marija Lesjak / Rukshana Hoque / Sara Balesaria / Vernon Skinner / Edward S Debnam / Surjit K S Srai / Paul A Sharp

PLoS ONE, Vol 9, Iss 7, p e

2014 Volume 102900

Abstract	Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin--the most abundant dietary polyphenol--are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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In stock of ZB MED Cologne/Königswinter

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Inter-library loan at ZB MED