scholarly journals Salvia miltiorrhiza (SM) Injection Ameliorates Iron Overload-Associated Cardiac Dysfunction by Regulating the Expression of DMT1, TfR1, and FP1 in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yuanyuan Zhang ◽  
Yucong Xue ◽  
Bin Zheng ◽  
Xue Han ◽  
Donglai Ma ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Uptake ◽  
Salvia Miltiorrhiza ◽  
Iron Deposition ◽  
Control Group ◽  
High Dose ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Cardiac Iron ◽  
Related Proteins

Previous studies have found that Salvia miltiorrhiza (SM) injection have a protective effect on the iron overloaded (IO) heart. However, the mechanisms are not completely known. In the present study, we investigated the underlying mechanisms based on the iron transport-related proteins. The rats were randomly divided into five groups: control, IO group, low-dose SM group, high-dose SM group, and deferoxamine control group. Iron dextran was injected to establish the IO model. After 14 days of treatment, cardiac histological changes were observed by hematoxylin and eosin (H&E) staining. Iron uptake-related proteins divalent metal transporter-1 (DMT-1), transferrin receptor-1 (TfR-1), and iron export-related proteins ferroportin1 (FP1) in the heart were detected by Western blotting. The results showed that SM injection decreased cardiac iron deposition, ameliorated cardiac function, and inhibited cardiac oxidation. Most important of all, SM injection downregulated the expression of DMT-1 and TfR-1 and upregulated FP1 protein levels compared with the IO group. Our results indicated that reducing cardiac iron uptake and increasing iron excretion may be one of the important mechanisms of SM injection reducing cardiac iron deposition and improving cardiac function under the conditions of IO.

Expression of iron-related proteins in the duodenum is up-regulated in patients with chronic inflammatory disorders

2013 ◽  
Vol 111 (6) ◽  
pp. 1059-1068 ◽  
Author(s):  
Abitha Sukumaran ◽  
Jithu James ◽  
Harish Palleti Janardhan ◽  
Anita Amaladas ◽  
Lekshmy Madathilazhikathu Suresh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Control Group ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Inflammatory Disorders ◽  
Inflammatory Conditions ◽  
Gene And Protein Expression ◽  
Fe Homeostasis ◽  
Related Proteins

Mechanisms responsible for derangements in Fe homeostasis in chronic inflammatory conditions are not entirely clear. The aim of the present study was to test the hypothesis that inflammation affects the expression of Fe-related proteins in the duodenum and monocytes of patients with chronic inflammatory disorders, thus contributing to dysregulated Fe homeostasis. Duodenal mucosal samples and peripheral blood monocytes obtained from patients with chronic inflammatory disorders, namely ulcerative colitis (UC), Crohn's disease (CD) and rheumatoid arthritis, were used for gene and protein expression studies. Hb levels were significantly lower and serum C-reactive protein levels were significantly higher in patients in the disease groups. The gene expression of several Fe-related proteins in the duodenum was significantly up-regulated in patients with UC and CD. In patients with UC, the protein expression of divalent metal transporter 1 and ferroportin, which are involved in the absorption of dietary non-haem Fe, was also found to be significantly higher in the duodenal mucosa. The gene expression of the duodenal proteins of interest correlated positively with one another and negatively with Hb. In patients with UC, the gene expression of Fe-related proteins in monocytes was found to be unaffected. In a separate group of patients with UC, serum hepcidin levels were found to be significantly lower than those in the control group. In conclusion, the expression of Fe-related proteins was up-regulated in the duodenum of patients with chronic inflammatory conditions in the present study. The effects appeared to be secondary to anaemia and the consequent erythropoietic drive.

Does Hepatic Hepcidin Play an Important Role in Exercise-Associated Anemia in Rats?

2011 ◽  
Vol 21 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Yu-Qian Liu ◽  
Yan-Zhong Chang ◽  
Bin Zhao ◽  
Hai-Tao Wang ◽  
Xiang-Lin Duan
Keyword(s):  
Regulatory Mechanism ◽  
Iron Absorption ◽  
White Blood Cells ◽  
Strenuous Exercise ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Transcriptional Level ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Sports Anemia

Some athletes are diagnosed as suffering from sports anemia because of iron deficiency, but the regulatory mechanism remains poorly understood. It is reported that hepcidin may provide a way to illuminate the regulatory mechanism of exercise-associated anemia. Here the authors investigate the hepcidin-involved iron absorption in exercise-associated anemia. Twelve male Wistar rats (300 ± 10 g) were randomly divided into 2 groups, 6 in a control group (CG) and 6 in an exercise group (EG, 5 wk treadmill exercise of different intensities with progressive loading). Serum samples were analyzed for circulating levels of IL-6 by means of enzyme-linked immunosorbent assay (ELISA). The expression of hepatic hepcidin mRNA was examined by real-time polymerase chain reaction analysis. The protein levels of divalent metal transporter 1 (DMT1), ferroportin1 (FPN1), and heme-carrier protein 1 (HCP1) of duodenum epithelium were examined by Western blot. The results showed that the amount of iron and ferritin in serum were lower in EG than in CG (p < .05). The levels of IL-6 and white blood cells were greater in EG than in CG (p < .01). The expression of DMT1, HCP1, and FPN1 was significantly lower in EG than in CG (p < .01). The mRNA expressions of hepatic hepcidin and hemojuvelin in skeletal muscle were remarkably higher in EG than in CG. The data indicated that inflammation was induced by strenuous exercise, and as a result, the transcriptional level of the hepatic hepcidin gene was increased, which further inhibited the expression of iron-absorption proteins and led to exercise-associated anemia.

Copper repletion enhances apical iron uptake and transepithelial iron transport by Caco-2 cells

2002 ◽  
Vol 282 (3) ◽  
pp. G527-G533 ◽  
Author(s):  
Okhee Han ◽  
Marianne Wessling-Resnick
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Cell Monolayer ◽  
Transepithelial Transport ◽  
Apical Surface ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Copper Status ◽  
Copper Supplementation

The influence of copper status on Caco-2 cell apical iron uptake and transepithelial transport was examined. Cells grown for 7–8 days in media supplemented with 1 μM CuCl2had 10-fold higher cellular levels of copper compared with control. Copper supplementation did not affect the integrity of differentiated Caco-2 cell monolayers grown on microporous membranes. Copper-repleted cells displayed increased uptake of iron as well as increased transport of iron across the cell monolayer. Northern blot analysis revealed that expression of the apical iron transporter divalent metal transporter-1 (DMT1), the basolateral transporter ferroportin-1 (Fpn1), and the putative ferroxidase hephaestin (Heph) was upregulated by copper supplementation, whereas the recently identified ferrireductase duodenal cytochrome b (Dcytb) was not. These results suggest that DMT1, Fpn1, and Heph are involved in the iron uptake process modulated by copper status. Although a clear role for Dcytb was not identified, an apical surface ferrireductase was modulated by copper status, suggesting that its function also contributes to the enhanced iron uptake by copper-repleted cells. A model is proposed wherein copper promotes iron depletion of intestinal Caco-2 cells, creating a deficiency state that induces upregulation of iron transport factors.

scholarly journals The Divalent Metal Transporter 1 (DMT1) Is Required for Iron Uptake and Normal Development of Oligodendrocyte Progenitor Cells

2018 ◽  
Vol 38 (43) ◽  
pp. 9142-9159 ◽  
Author(s):  
Veronica T. Cheli ◽  
Diara A. Santiago González ◽  
Leandro N. Marziali ◽  
Norma N. Zamora ◽  
María E. Guitart ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Iron Uptake ◽  
Normal Development ◽  
Divalent Metal ◽  
Oligodendrocyte Progenitor Cells ◽  
Divalent Metal Transporter 1 ◽  
Oligodendrocyte Progenitor ◽  
Divalent Metal Transporter ◽  
Metal Transporter

scholarly journals Hepcidin inhibits apical iron uptake in intestinal cells

2008 ◽  
Vol 294 (1) ◽  
pp. G192-G198 ◽  
Author(s):  
Natalia P. Mena ◽  
Andrés Esparza ◽  
Victoria Tapia ◽  
Pamela Valdés ◽  
Marco T. Núñez
Keyword(s):  
Iron Uptake ◽  
Basolateral Membrane ◽  
Intestinal Cells ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Cell Monolayers ◽  
Metal Transporter ◽  
Protein Levels ◽  
J774 Cells ◽  
Iron Export

Hepcidin (Hepc) is considered a key mediator in iron trafficking. Although the mechanism of Hepc action in macrophages is fairly well established, much less is known about its action in intestinal cells, one of the main targets of Hepc. The current study investigated the effects of physiologically generated Hepc on iron transport in Caco-2 cell monolayers and rat duodenal segments compared with the effects on the J774 macrophage cell line. Addition of Hepc to Caco-2 cells or rat duodenal segments strongly inhibited apical 55Fe uptake without apparent effects on the transfer of 55Fe from the cells to the basolateral medium. Concurrently, the levels of divalent metal transporter 1 (DMT1) mRNA and protein in Caco-2 cells decreased while the mRNA and protein levels of the iron export transporter ferroportin did not change. Plasma membrane localization of ferroportin was studied by selective biotinylation of apical and basolateral membrane domains; Hepc induced rapid internalization of ferroportin in J774 cells but not in Caco-2 cells These results indicate that the effect of Hepc is cell dependent: in macrophages it inhibits iron export by inducing ferroportin degradation, whereas in enterocytes it inhibits apical iron uptake by inhibiting DMT1 transcription. Our results highlight the crucial role of Hepc in the control of intestinal iron absorption.

Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3985-3987 ◽  
Author(s):  
Monika Priwitzerova ◽  
Guangjun Nie ◽  
Alex D. Sheftel ◽  
Dagmar Pospisilova ◽  
Vladimir Divoky ◽  
...  
Keyword(s):  
Protein Expression ◽  
Iron Uptake ◽  
Chinese Hamster ◽  
Microcytic Anemia ◽  
Homozygous Mutation ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Hypochromic Microcytic Anemia ◽  
Functional Consequences ◽  
Uptake Activity

We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G > C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expression and function. In contrast, deletion of exon 12 led to a decreased expression of the protein and disruption of its subcellular localization and iron uptake activity. We hypothesize that the residual protein in hematopoietic cells represents the functional E399D DMT1 variant, but because of its quantitative reduction, the iron uptake activity of DMT1 in the patient's erythroid cells is severely suppressed.

scholarly journals Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Yu ◽  
Huirong Sun ◽  
Wenliang Zha ◽  
Weili Cui ◽  
Ling Xu ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Injury ◽  
Serum Levels ◽  
Mtor Pathway ◽  
Cardiomyocyte Apoptosis ◽  
Control Group ◽  
Limiting Factor ◽  
High Dose ◽  
Induced Apoptosis ◽  
Related Proteins

Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg−1), and high-dose API treatment group (250 mg·kg−1). Blood samples were taken to evaluate a spectrum of myocardial enzymes. Cardiomyocyte apoptosis was measured using a TUNEL assay, and cardiomyocyte autophagy was observed using electron microscopy. Moreover, apoptosis-related proteins, such as Bax and Bcl-2, autophagy-related proteins, including Beclin1 and LC3B, and PI3K/AKT/mTOR pathway-related proteins were examined with western blot. Our results demonstrate that ADR caused an increase in the serum levels of cardiac injury markers and enhanced cardiomyocyte apoptosis and autophagy. API administration prevented the effects associated with ADR-induced cardiotoxicity in mice and inhibited ADR-induced apoptosis and autophagy. API also promoted PI3K/AKT/mTOR pathway activity in ADR-treated mice. In conclusion, API may have a protective effect against ADR-induced cardiotoxicity by inhibiting apoptosis and autophagy via activation of the PI3K/AKT/mTOR pathway.

scholarly journals Antitumor activity of tanshinone and its nanoparticles on U14 cervical carcinoma-bearing mice

2016 ◽  
Vol 3 ◽  
pp. 184954351667344
Author(s):  
Ya Di ◽  
Qingjie Meng ◽  
Hongwei Yang ◽  
Kun Li ◽  
Liyan Cao ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Cervical Carcinoma ◽  
Antitumor Effect ◽  
Salvia Miltiorrhiza ◽  
Control Group ◽  
High Dose ◽  
Tumor Inhibition ◽  
Malondialdehyde Content ◽  
Model Control ◽  
Model Control Group

In this study, tanshinone was extracted from Salvia miltiorrhiza. To improve the utilization and the dissolution of the drug, the tanshinone extractions were prepared at a pharmaceutical nanoscale and in the nanometer range of 100–200 nm. Then, the rate of tumor inhibition and the activity of antioxidant system and the thymus/spleen indices were investigated to find the antitumor effect of nanoparticles of tanshinone in cervical carcinoma-bearing mice. Our data suggest that tanshinone inhibits cervical tumor growth and the rates of tumor inhibition of all drug groups were more than 45%. The highest rate was 70.88% in the high dose of nanoscale tanshinone group. The activities of superoxide dismutase were higher in drug groups than in the model control group, and the concentrations of malondialdehyde were significantly lower. These findings suggested that tanshinone enhance the superoxide dismutase activity of the mice and decrease the malondialdehyde content. It may be one of the mechanisms of antitumor effect of tanshinone. The thymus index and spleen index were higher than normal control or model control. These data suggested that tanshinone also enhanced the immune system of mice.

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