Influence of Hepcidin in the Development of Anemia

Reichert, Cadiele Oliana; Marafon, Filomena; Levy, Débora; Maselli, LucianaMorganti Ferreira; Bagatini, Margarete Dulce; LúciaBlatt, Solange; Bydlowski, Sérgio Paulo; Spada, Celso

doi:10.5772/intechopen.71476

Cited by 4 publications

(6 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transferrin is responsible for the transport of ferric iron in the body and ferritin for the storage of iron [39,40]. Besides, transferrin and ferritin are also acute phase proteins.…”

Section: Discussionmentioning

confidence: 99%

Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease

et al. 2019

Self Cite

View full text Add to dashboard Cite

(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender. PON-1 activities (arylesterase and paraoxonase) were determined by enzymatic hydrolysis of phenylcetate and paraoxon, respectively. Polymorphisms were determined by Restriction Fragment Length Polymorphism- Polymerase Chain Reaction (RFLP-PCR). (3) Results: Plasma cholesterol and fractions, ApoA1 and ApoB levels were all decreased in sickle cell disease patients, while anti-oxidized low-density lipoprotein (LDL) antibodies and C-reactive protein were increased. Serum arylesterase activity was lower in sickle cell disease patients when compared with healthy controls. In patients, paraoxonase activity was higher in those with PON-1 RR Q192R polymorphism. In these patients, the increase of serum iron and ferritin levels and transferrin saturation were less pronounced than those observed in patients with QQ or QR polymorphism. No differences were observed with PON-1 L55M, and PON-2 and PON-3 polymorphisms. Multivariate regression analysis showed that transferrin and ferritin concentrations correlated with arylesterase and paraoxonase activities. (4) Conclusions: Both transferrin and ferritin were the main predictors of decreased arylesterase and paraoxonase activities in patients with sickle cell disease. LDL oxidation increased, and RR PON-1 Q192R polymorphism is likely to be a protective factor against oxidative damage in these patients.

show abstract

“…Transferrin is responsible for the transport of ferric iron in the body and ferritin for the storage of iron [39,40]. Besides, transferrin and ferritin are also acute phase proteins.…”

Section: Discussionmentioning

confidence: 99%

Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Fe 3+ /Fe 2+ redox potential participates in a large number of protein complexes, especially those that involve oxygen reduction for adenosine triphosphate (ATP) synthesis and the reduction of DNA precursors. Iron is also a necessary component in the formation of molecules that bind and transport oxygen (hemoglobin and myoglobin) and for the activities of cytochrome enzymes, as well as in many enzymes that perform the redox process, functioning as electron carriers [ 83 , 84 , 85 ].…”

Section: Ferroptosismentioning

confidence: 99%

“…When necessary, iron stocks are mobilized and exported by ferroportin (FPN). This process is downregulated by hepcidin [ 83 , 84 , 85 ].…”

Section: Ferroptosismentioning

confidence: 99%

See 1 more Smart Citation

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Reichert

Freitas

Sampaio-Silva

et al. 2020

IJMS

Self Cite

252

148

View full text Add to dashboard Cite

Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, and Huntington’s diseases, has also been addressed.

show abstract

“…Research has shown that hepcidin mostly expressed by the hepatocytes is stimulated by iron overload (mediated through the bone morphogenetic protein (BMP) signalling pathway) and inflammation (by interleukin 6 (IL-6) and other cytokines through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway), whereas erythropoietic activity, anaemia or hypoxia suppress its synthesis [ 15 , 16 ]. Hepcidin and ferroportin form a complex, which is absorbed by these cells, where it causes ferroportin to degrade, inhibiting iron outflow and, as a result, reducing intestinal iron absorption and bioavailability [ 17 ]. Similar to other genes, various mutations in the HAMP gene have been reported.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of HAMP rs10421768 gene and phenotypic expression of hepcidin; a case-control study among sickle cell anaemia patients in Ghana

Appiah,

Nkansah,

Abbam

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Background The sporadic nature of blood transfusion therapy coupled with the alteration of HAMP genes may exacerbate the risk of iron burden in sickle cell anaemia (SCA) patients. The study determined the polymorphic distribution of the HAMP promoter gene rs10421768 and hepcidin levels in SCA patients. Method Sixty participants aged ≥12years [45 SCA patients and 15 controls (HbA)] were recruited from 15th March, 2023 to 20th July, 2023 for a case-control study at Methodist Hospital Wenchi, Ghana. Complete blood count and hepcidin levels assessment were done using haematology analyzer and ELISA, respectively. Genomic DNA was extracted using the Qiagen Kit, and HAMP gene rs10421768 (c.-582 A>G) was sequenced using the MassARRAY method. Data were analysed using SPSS version 26.0. Results The frequencies of the HAMP promoter rs10421768 genotypes AA, AG, and GG were 64.4%, 33.3%, and 2.2% in SCA patients, and 86.7%, 13.3%, and 0% in the controls, respectively. Serum hepcidin levels were significantly higher among controls than cases [204.0 (154.1–219.3) vs 150.2 (108.1–195.6)μg/L, p<0.010]. Participants with HAMP rs10421768 homozygous A genotype had higher serum levels of hepcidin compared with those in the wild genotypes (AG/GG) group [(188.7 (130.9–226.9) vs 136.8 (109.7–157.8)μg/L, p<0.016]. Disease severity and blood cell parameters were not associated with the HAMP variants (p>0.05). Conclusion The HAMP promoter rs10421768 AA genotype has the highest frequency of distribution and the GG genotype with the least distribution. Participants with HAMP rs10421768 G allele (c.-582A>G) had reduced levels of hepcidin. HAMP rs10421768 genotypes had no association with blood cell parameters and disease severity. The HAMP rs10421768 genotypes may influence serum levels of hepcidin. Further study is required to elucidate the potential effect of the G allele on hepcidin transcription.

show abstract

Influence of Hepcidin in the Development of Anemia

Cited by 4 publications

References 67 publications

Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease

Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Molecular characterization of HAMP rs10421768 gene and phenotypic expression of hepcidin; a case-control study among sickle cell anaemia patients in Ghana

Contact Info

Product

Resources

About