scholarly journals Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258433
Author(s):  
Supathra Phoaubon ◽  
Kornkamon Lertsuwan ◽  
Jarinthorn Teerapornpuntakit ◽  
Narattaphol Charoenphandhu
Keyword(s):  
Iron Uptake ◽  
Calcium Uptake ◽  
Calcium Absorption ◽  
Ammonium Citrate ◽  
Intestinal Cell ◽  
Cell Calcium ◽  
Iron Transporter ◽  
Transporter Expression ◽  
Iron And Calcium ◽  
Calcium Transporter

Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transport. However, whether this effect could be replicated in other conditions is not known. Therefore, this study aimed to investigate the effects of hepcidin on iron and calcium uptake ability under physiological, iron uptake stimulation and calcium uptake suppression. To investigate the potential mechanism, effects of hepcidin on the expression of iron and calcium transporter and transport-associated protein in Caco-2 cells were also determined. Our results showed that intestinal cell iron uptake was significantly increased by ascorbic acid together with ferric ammonium citrate (FAC), but this phenomenon was suppressed by hepcidin. Interestingly, hepcidin significantly increased calcium uptake under physiological condition but not under iron uptake stimulation. While hepcidin significantly suppressed the expression of iron transporter, it had no effect on calcium transporter expression. This indicated that hepcidin-induced intestinal cell calcium uptake did not occur through the stimulation of calcium transporter expression. On the other hand, 1,25(OH)2D3 effectively induced intestinal cell calcium uptake, but it did not affect intestinal cell iron uptake or iron transporter expression. The 1,25(OH)2D3-induced intestinal cell calcium uptake was abolished by 12 mM CaCl2; however, hepcidin could not rescue intestinal cell calcium uptake suppression by CaCl2. Taken together, our results showed that hepcidin could effectively and concurrently induce intestinal cell calcium uptake while reducing intestinal cell iron uptake under physiological and iron uptake stimulation conditions, suggesting its therapeutic potential for inactive calcium absorption, particularly in thalassemic patients or patients who did not adequately respond to 1,25(OH)2D3.

165 EXPRESSION OF CALCIUM TRANSPORTER 1 GENE IN THE UTERUS OF RATS DURING PREGNANCY

2007 ◽  
Vol 19 (1) ◽  
pp. 199
Author(s):  
B.-M. Lee ◽  
G.-S. Lee ◽  
E.-B. Jeung
Keyword(s):  
Calcium Uptake ◽  
Calcium Absorption ◽  
Reproductive Organs ◽  
Sprague Dawley ◽  
Uterine Smooth Muscle ◽  
Vaginal Plug ◽  
Sprague Dawley Rats ◽  
Insight Into ◽  
Calcium Transporter ◽  
Relevant Factors

Calcium Transporter 1 (CaT1), which is highly expressed in calcium-absorption organs, i.e. duodenum and kidney, is a critical mediator for calcium uptake during transcellular calcium transport. It has been shown that CaT1 gene is also expressed in the placenta and uterine smooth muscle in female reproductive organs. We previously demonstrated that uterine CaT1 mRNA is highly expressed at diestrus and tightly regulated by progesterone (P4) related to calcium homeostasis for uterine functions during the estrous cycle in rats. Thus, in the recent study, we further examined the expression of CaT1 mRNA in the uterus and placenta of rats to elucidate its role during pregnancy in these tissues. Female Sprague Dawley rats (n = 2) were employed and their pregnancy days (PD) were determined by a vaginal plug every morning; the rats were euthanized daily (PD 0 to 21). The expression of CaT1 mRNA decreased from PD 0 to 4 and highly increased on PD 5 to 10. Its increased transcripts gradually decreased at the end of pregnancy. Taken together, these results indicate that the expression level of CaT1 mRNA is regulated in the uterus of rats during pregnancy, probably via sex steroid hormones and their receptors through a complex pathway. A further study is warranted to verify relevant factors which regulate CaT1 gene and to provide further insight into its role(s) in the female reproductive tissues.

scholarly journals Zinc induces iron uptake and DMT1 expression in Caco-2 cells via a PI3K/IRP2 dependent mechanism

2019 ◽  
Vol 476 (11) ◽  
pp. 1573-1583 ◽  
Author(s):  
Palsa Kondaiah ◽  
Mohamad F. Aslam ◽  
Purna Chandra Mashurabad ◽  
Paul A. Sharp ◽  
Raghu Pullakhandam
Keyword(s):  
Protein Expression ◽  
Iron Uptake ◽  
Iron Absorption ◽  
Pi3k Pathway ◽  
Intestinal Cell ◽  
Zinc Treatment ◽  
Akt Phosphorylation ◽  
Iron Transporter ◽  
Sirna Silencing ◽  
Dependent Mechanism

Abstract The absorption of iron is influenced by numerous dietary and physiological factors. We have previously demonstrated that zinc treatment of intestinal cells increases iron absorption via induction of the apical membrane iron transporter divalent metal ion transporter-1 (DMT1). To better understand the mechanisms of zinc-induced iron absorption, we have studied the effect of zinc on iron uptake, iron transporter and iron regulatory protein (IRP 1 and 2) expression and the impact of the PI3K pathway in differentiated Caco-2 cells, an intestinal cell culture model. We found that zinc induces DMT1 protein and mRNA expression. Zinc-induced DMT1 expression and iron absorption were inhibited by siRNA silencing of DMT1. Furthermore, zinc treatment led to increased abundance of IRP2 protein in cell lysates and in polysomal fractions, implying its binding to target mRNAs. Zinc treatment induced Akt phosphorylation, indicating the activation of the PI3K pathway. LY294002, a specific inhibitor of PI3K inhibited zinc-induced Akt phosphorylation, iron uptake, DMT1 and IRP2 expression. Furthermore, LY294002 also decreased the basal level of DMT1 mRNA but not protein expression. siRNA silencing of IRP2 led to down-regulation of both basal and zinc-induced DMT1 protein expression, implying possible involvement of post-transcriptional regulatory mechanisms. In agreement with these findings, zinc treatment stabilized DMT1 mRNA levels in actinomycin D-treated cells. Based on these findings, we conclude that zinc-induced iron absorption involves elevation of DMT1 expression by stabilization of its mRNA, by a PI3K/IRP2-dependent mechanism.

scholarly journals Calcium uptake and calcium transporter expression by trophoblast cells from human term placenta

2002 ◽  
Vol 1564 (2) ◽  
pp. 325-332 ◽  
Author(s):  
Robert Moreau ◽  
Georges Daoud ◽  
Renée Bernatchez ◽  
Lucie Simoneau ◽  
André Masse ◽  
...  
Keyword(s):  
Calcium Uptake ◽  
Trophoblast Cells ◽  
Human Term Placenta ◽  
Term Placenta ◽  
Transporter Expression ◽  
Calcium Transporter

scholarly journals A role for tumour necrosis factor α in human small bowel iron transport

2005 ◽  
Vol 390 (2) ◽  
pp. 437-446 ◽  
Author(s):  
Naveen Sharma ◽  
Abas H. Laftah ◽  
Matthew J. Brookes ◽  
Brian Cooper ◽  
Tariq Iqbal ◽  
...  
Keyword(s):  
Small Bowel ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Iron Transport ◽  
Tumour Necrosis Factor Α ◽  
Iron Transporter ◽  
Factor Α ◽  
Transporter Expression ◽  
Necrosis Factor ◽  
Iron Export

Cytokines are integral to the development of anaemia of chronic inflammation. Cytokines modulate hepcidin expression and iron sequestration by the reticuloendothelial system but their direct effects on small bowel iron transport are not well characterized. The aim of the present study was to examine the local effects of TNFα (tumour necrosis factor α) on small bowel iron transport and on iron transporter expression in the absence of hepcidin. The effects of TNFα on iron transport were determined using radiolabelled iron in an established Caco-2 cell model. The effect of TNFα on the expression and localization of the enterocyte iron transporters DMT-1 (divalent metal transporter 1), IREG-1 (iron-regulated transporter 1) and ferritin was determined utilizing Caco-2 cells and in a human ex vivo small bowel culture system. TNFα mediated an early induction in both iron import and iron export, which were associated with increased DMT-1 and IREG-1 mRNA and protein expression (P<0.05). However, by 24 h, both iron import and iron export were significantly inhibited, coinciding with an induction of ferritin heavy chain (P<0.05) and a decrease in DMT-1 and IREG-1 to baseline levels. In addition, there was a relocalization of IREG-1 away from the basolateral cell border and increased iron deposition in villous enterocytes. In conclusion, TNFα has a direct effect on small bowel iron transporter expression and function, leading to an inhibition of iron transport.

Caseinphosphopeptide-induced calcium uptake in human intestinal cell lines HT-29 and Caco2 is correlated to cellular differentiation☆

2010 ◽  
Vol 21 (3) ◽  
pp. 247-254 ◽  
Author(s):  
Stefania Cosentino ◽  
Claudia Gravaghi ◽  
Elena Donetti ◽  
Bianca M. Donida ◽  
Giovanni Lombardi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cellular Differentiation ◽  
Calcium Uptake ◽  
Intestinal Cell ◽  
Ht 29 ◽  
Intestinal Cell Lines
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