Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8

Upanan, Supranee; McKie, Andrew T.; Latunde-Dada, Gladys O.; Roytrakul, Sittiruk; Uthaipibull, Chairat; Pothacharoen, Peraphan; Kongtawelert, Prachya; Fucharoen, Suthat; Srichairatanakool, Somdet

doi:10.1007/s12185-017-2231-3

Cited by 5 publications

(5 citation statements)

References 54 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, green tea polyphenols and curcuminoids present in the drink could possibly interfere absorption of dietary iron and mobilize delivery of iron to the erythrons [65,79,119]. Taken all our studies, we summarize the applications of nutraceutical green tea extract for the amelioration of iron-overloaded cells, β-thalassemic mice, and patients with β-thalassemia (Figure 5) [79,84,106,116,[119][120][121][122][123][124][125][126][127][128]. In our expectations, we hope the patients will have safer chelation therapy, a better quality of lives, and good health.…”

Section: Patients With β-Thalassemiamentioning

confidence: 77%

Nutraceutical Benefits of Green Tea in Beta-Thalassemia with Iron Overload

Koonyosying¹,

Fucharoen²,

Srichairatanakool³

2020

Beta Thalassemia

Self Cite

View full text Add to dashboard Cite

Secondary iron overload in patients with β-thalassemia is caused by multiple blood transfusions and increased iron absorption. Most of them die from cardiac arrest and infections while others from oxidative tissue damage and organ dysfunction. Under high saturation of transferrin with iron, redox-active iron such as nontransferrin-bound iron, labile plasma iron, and cellular labile iron pool is prone to the production of reactive oxygen species, oxidized biomolecules, oxidative tissue damages, and complications. Iron chelation therapy and antioxidant supplementation are a supportive treatment for patients' better quality of life and life expectancy. Green tea (Camellia sinensis) extract (GTE) is abundant with polyphenols, mainly epigallocatechin-3-gallate and nutraceuticals, which are beneficial for cell functions and health. Importantly, GTE possesses antioxidant, free radical scavenging, metal-chelating, anti-hemolysis properties in cell cultures, animals, and humans. This article has reported modes of actions and challenged such wonderful properties of green tea used to remove excessive iron, scavenge harmful radicals, restore malfunctions of vital organs, and treat patients with β-thalassemia with iron overload. Infeasibility and sustainability, the benefits of green tea can be applied for use in other diseases with iron toxicity and oxidative stress.

show abstract

Section: Patients With β-Thalassemiamentioning

confidence: 77%

Nutraceutical Benefits of Green Tea in Beta-Thalassemia with Iron Overload

Koonyosying¹,

Fucharoen²,

Srichairatanakool³

2020

Beta Thalassemia

Self Cite

View full text Add to dashboard Cite

show abstract

“…ATOH8 gene, is a positive regulator of hepcidin transcription in the liver, which maintains iron homeostasis through regulating its own synthesis 20 . It has been reported that, hepcidin and ATOH8 expressions are downregulated in β thalassemia mice 21 . Mutation in this gene may causes the iron overload in the subject.…”

Section: Resultsmentioning

confidence: 98%

A Family Based Whole Exome Sequence Study to Indentify Modifier Genes for Phenotype Heterogeneity Between Severe and Non-Severe Thalassemia Patients

BASU¹,

Saha²,

Chowdhury³

et al. 2023

Preprint

View full text Add to dashboard Cite

Thalassemia is a common monogenic autosomal disorder prevalent in India. HbE beta thalassemia is a compound heterozygous state of two different beta globin mutations (HBB), predominant in the Eastern India. In HbE-beta thalassemia (β+/β°) patients, one HBB mutation does not produce any functional protein (β°); another mutation produces a structural altered haemoglobin, variant E (β+). It has been observed that in HbE-beta thalassemia patients with same type of HBB mutations, there exist diverse phenotypic presentation ranging from very severe, with regular transfusion-dependence to clinically non severe requiring very less transfusion or no transfusion. To explore this phenotypic mystery, we performed trio based expanded whole exome sequencing (WES) of two extreme phenotypes of HbE beta thalassemia subjects with similar HBB genotype and their parents. For WES library preparation, Agilent Sure select V6+UTR kit was used and sequencing was done through the Illumina HiSeq 2500 platform. This study aimed to search for de novo or inherited variants associated with the clinical severity. Six significant inherited variants were found in the genes, ATOH8, TTLL4, P2RX7, PRSS54, SLC9C2 and VRK2 in severe subject, however only one significant inherited variant in MTRR gene was found in non-severe subject. Bioinformatic analysis also confirms that each variant significantly changes in respective protein structure. The identified genes were either associated with iron absorption, oxidative stress, hematopoietic stem cell differentiation, structural organization of RBC cytoskeleton or regulating anemia. No significant de novo variant were identified associated with clinical severity. The finding of this study indicates that the combined effect of mutation load in major pathways may responsible for severe phenotype.

show abstract

“…We have previously demonstrated that hepatic Hamp1 mRNA suppression is associated with a down−regulation of atonal homolog 8, which is a positive regulator of hepcidin transcription that links erythropoiesis with iron−responsive molecules in response to iron−loading anemias (e.g., thalassemia) (Upanan et al, 2015). Inversely, the Hamp1 expression was significantly up−regulated in the BKO mice treated with a combination of GTE and DFP (Upanan et al, 2017). Interestingly, Kim and colleagues showed that EGCG treatment induced expression and its production of small heterodimer partner-interacting leucine zipper protein in hepatocytes, subsequently turning on bone morphogenetic protein 6−mediated SMAD1/5/8 transactivation of the hepcidin gene, and consequently increasing the hepcidin secretion from the hepatocytes (Kim et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Effects of green tea extract treatment on erythropoiesis and iron parameters in iron-overloaded β-thalassemic mice

et al. 2022

Self Cite

View full text Add to dashboard Cite

β-Thalassemia is characterized by ineffective erythropoiesis leading to chronic anemia. Thus, increased iron absorption from the duodenum and via blood transfusions is required to maintain normal blood hemoglobin (Hb) levels and iron chelators in the removal of excessive iron. Certain agents are also needed for the improvement of stress erythropoiesis and iron dysregulation. Green tea extract (GTE), which is rich in epigallocatechin-3-gallate (EGCG), is known to possess radical scavenging and iron-chelating activities. We aimed to assess the effects of green tea extract on erythroid regulators, iron mobilization and anti–lipid peroxidation in the liver, spleen, and kidneys of iron-loaded β-globin gene knockout thalassemic (BKO) mice. Our results indicate that treatments of green tea extract and/or deferiprone (DFP) diminished levels of plasma erythropoietin (EPO) and erythroferrone (ERFE), and consistently suppressed kidney Epo and spleen Erfe mRNA expressions (p < .05) in iron- loaded BKO mice when compared with untreated mice. Coincidently, the treatments decreased plasma ferritin (Ft) levels, iron content levels in the liver (p < .05), spleen (p < .05), and kidney tissues of iron–loaded BKO mice. Furthermore, lipid-peroxidation products in the tissues and plasma were also decreased when compared with untreated mice. This is the first evidence of the orchestral role of green tea extract abundant with epigallocatechin-3-gallate in improving ineffective erythropoiesis, iron dysregulation and oxidative stress in iron-overloaded β-thalassemic mice.

show abstract

Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8

Cited by 5 publications

References 54 publications

Nutraceutical Benefits of Green Tea in Beta-Thalassemia with Iron Overload

Nutraceutical Benefits of Green Tea in Beta-Thalassemia with Iron Overload

A Family Based Whole Exome Sequence Study to Indentify Modifier Genes for Phenotype Heterogeneity Between Severe and Non-Severe Thalassemia Patients

Effects of green tea extract treatment on erythropoiesis and iron parameters in iron-overloaded β-thalassemic mice

Contact Info

Product

Resources

About