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Myeloid specific deletion of ferroportin impairs macrophage bioenergetics but is disconnected from systemic insulin action in adult mice
Am J Physiol Endocrinol Metab. 2021 Aug 2. doi: 10.1152/ajpendo.00116.2021. Online ahead of print.ABSTRACTTissue iron overload is associated with insulin resistance and mitochondrial dysfunction in rodents and humans; however, the mechanisms or cell types that mediate this phenotype are not completely understood. Macrophages (Mɸ)s are known to contribute to iron handling; thus, we hypothesized that perturbed iron handling by Mɸs impairs mitochondrial energetics and evokes systemic insulin resistance in mice. Male and female mice with myeloid targeted (LysMCre) deletion of the canonical iron exporter, ferroportin (Fpn, en...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 2, 2021 Category: Physiology Authors: Nathan C Winn Elysa M Wolf Matthew A Cottam Monica Bhanot Alyssa H Hasty Source Type: research
Ferroportin-mediated ferroptosis involved in new-onset atrial fibrillation with LPS-induced endotoxemia
This study aims to investigate the underlying mechanisms linking ferroptosis and AF caused by sepsis. LPS-induced endotoxemia is often used to model the acute inflammatory response associated with sepsis. Herein, we reported that ferroptosis was significantly activated in LPS-induced endotoxemia rat model. We also observed that ferroportin (Fpn), the only identified mammalian non-heme iron exporter, was downregulated in the atrium of endotoxemia model. Vulnerability to AF was also significantly increased in a endotoxemia rat model. Additionally, Fpn knockdown by shFpn further increased intracellular iron concentration and ...
Source: European Journal of Pharmacology - November 8, 2021 Category: Drugs & Pharmacology Authors: Jin Fang Bin Kong Wei Shuai Zheng Xiao Chang Dai Tianyou Qin Yang Gong Jun Zhu Qi Liu He Huang Source Type: research
Minimal effect of conditional ferroportin KO in the neural retina implicates ferrous iron in retinal iron overload and degeneration
Exp Eye Res. 2022 Feb 21:108988. doi: 10.1016/j.exer.2022.108988. Online ahead of print.ABSTRACTIron-induced oxidative stress can cause or exacerbate retinal degenerative diseases. Retinal iron overload has been reported in several mouse disease models with systemic or neural retina-specific knockout (KO) of homologous ferroxidases ceruloplasmin (Cp) and hephaestin (Heph). Cp and Heph can potentiate ferroportin (Fpn) mediated cellular iron export. Here, we used retina-specific Fpn KO mice to test the hypothesis that retinal iron overload in Cp/Heph DKO mice is caused by impaired iron export from neurons and glia. Surprisin...
Source: Experimental Eye Research - February 24, 2022 Category: Opthalmology Authors: Yingrui Liu Bailey Baumann Ying Song Kevin Zhang Jacob K Sterling Samira Lakhal-Littleton Zbynek Kozmik Guanfang Su Joshua L Dunaief Source Type: research
Ferroportin inhibitor vamifeport ameliorates ineffective erythropoiesis in a mouse model of β-thalassemia with blood transfusions
Haematologica. 2023 May 11. doi: 10.3324/haematol.2022.282328. Online ahead of print.ABSTRACTβ-thalassemia is an inherited anemia characterized by ineffective erythropoiesis. Blood transfusions are required for survival in transfusion-dependent β-thalassemia and are also occasionally needed in patients with non-transfusion-dependent β-thalassemia. Patients with transfusion-dependent β-thalassemia often have elevated transferrin saturation (TSAT) and non-transferrin-bound iron (NTBI) levels, which can lead to organ iron overload, oxidative stress, and vascular damage. Vamifeport is an oral ferroportin inhibitor that was...
Source: Haematologica - May 11, 2023 Category: Hematology Authors: Natarajaswamy Kalleda Anna Flace Patrick Altermatt Giada Ingoglia C édric Doucerain Naja Nyffenegger Franz D ürrenberger Vania Manolova Source Type: research
A convenient luminescent assay of ferroportin internalization to study its interaction with hepcidin
Hepcidin is a liver‐secreted small disulfide‐rich peptide that plays a key role in iron homeostasis by binding and mediating the internalization and degradation of the so far only known iron efflux transporter ferroportin (Fpn). To study hepcidin‐Fpn interactions, in the present work we established a convenient luminescent assay for the quantitative measurement of hepcidin‐induced Fpn internalization by fusing a small nanoluciferase (NanoLuc, 171 amino acids) at the Fpn C‐terminus. Once the NanoLuc‐tagged Fpn was internalized, the measured luminescence was significantly decreased when assayed using the intact t...
Source: FEBS Journal - February 1, 2013 Category: Research Authors: Ge Song, Qian Jiang, Ting Xu, Ya‐Li Liu, Zeng‐Guang Xu, Zhan‐Yun Guo Tags: Original Article Source Type: research
Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection
In this study, we found that NO up-regulated the expression of ferroportin-1 (Fpn1), the major cellular iron exporter, in mouse and human cells. Nos2–/– macrophages displayed increased iron content due to reduced Fpn1 expression and allowed for an enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Nos2 gene disruption or inhibition of NOS2 activity led to an accumulation of iron in the spleen and splenic macrophages. Lack of NO formation resulted in impaired nuclear factor erythroid 2-related factor-2 (Nrf2) expression, resulting in reduced Fpn1 transcription and diminished cellula...
Source: The Journal of Experimental Medicine - May 6, 2013 Category: Internal Medicine Authors: Nairz, M., Schleicher, U., Schroll, A., Sonnweber, T., Theurl, I., Ludwiczek, S., Talasz, H., Brandacher, G., Moser, P. L., Muckenthaler, M. U., Fang, F. C., Bogdan, C., Weiss, G. Tags: Articles Source Type: research
SLC40A1-R178G or R178Q and ferroportin disease? A call for vigilance in mutation reporting
I refer to a previous Letter to the Editor and its reply regarding the excellent meta-analysis on ferroportin disease performed by Mayr et al. in the Journal of Hepatology in November 2010 . The SLC40A1-R178G mutation is discussed and whether it is a disease-causing mutation with incomplete penetrance or a polymorphism. Upon further inspection of the original report by Speletas et al., describing the R178G mutation in a Greek family, published in the journal Blood Cell Molecules and Diseases in 2008 , I have come to the conclusion that an error was made in the designation of this mutation. Rather than an arginine to glycin...
Source: Journal of Hepatology - March 21, 2013 Category: Gastroenterology Authors: Daniel F. Wallace Tags: Letters to the Editor Source Type: research
