A5084293080- Heme Oxygenase-1 and Carbon Monoxide
- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Porphyrin Metabolism and Disorders
- Metabolism and Genetic Disorders
- Iron Metabolism and Disorders
- Neurological diseases and metabolism
- RNA modifications and cancer
- Hemoglobin structure and function
- Neonatal Health and Biochemistry
- Cancer, Hypoxia, and Metabolism
- Diet and metabolism studies
- Erythropoietin and Anemia Treatment
- Mitochondrial Function and Pathology
- Genomics, phytochemicals, and oxidative stress
- Hereditary Neurological Disorders
- Endoplasmic Reticulum Stress and Disease
- Trace Elements in Health
- Epigenetics and DNA Methylation
- Metabolism, Diabetes, and Cancer
- Cannabis and Cannabinoid Research
- RNA regulation and disease
- Kruppel-like factors research
- Cancer Treatment and Pharmacology
- Alzheimer's disease research and treatments
University of Turin
2015-2024
Odense University Hospital
2016
Macrophages of the reticuloendothelial system play a key role in recycling iron from hemoglobin senescent or damaged erythrocytes. Heme oxygenase 1 degrades heme moiety and releases inorganic that is stored ferritin exported to plasma via export protein ferroportin. In plasma, binds transferrin made available for de novo red cell synthesis. The aim this study was gain insight into regulatory mechanisms control transcriptional response ferroportin macrophages.Iron mRNA expression analyzed...
Feline leukemia virus subgroup C receptor 1 (FLVCR1) is a cell membrane heme exporter that maintains the balance between levels and globin synthesis in erythroid precursors. It was previously shown Flvcr1-null mice died utero due to failure of erythropoiesis. Here, we identify Flvcr1b, mitochondrial Flvcr1 isoform promotes efflux into cytoplasm. Flvcr1b overexpression promoted vitro differentiation, whereas silencing caused accumulation termination differentiation. Furthermore, lacking...
Heme is required for cell respiration and survival. Nevertheless, its intracellular levels need to be finely regulated avoid heme excess, which may catalyze the production of reactive oxygen species (ROS) promote death. Here, we show that alteration homeostasis in endothelial cells due loss exporter FLVCR1a, results impaired angiogenesis. In vitro, FLVCR1a silencing causes defective tubulogenesis poor viability accumulation. Consistently, endothelial-specific Flvcr1a knockout mice aberrant...
Heme is an iron-containing porphyrin of vital importance for cell energetic metabolism. High rates heme synthesis are commonly observed in proliferating cells. Moreover, the cell-surface exporter feline leukemia virus subgroup C receptor 1a (FLVCR1a) overexpressed several tumor types. However, reasons why and export enhanced highly cells remain unknown. Here, we illustrate a functional axis between export: efflux through plasma membrane sustains synthesis, implementation two processes...
The liver has one of the highest rates heme synthesis any organ. More than 50% synthesized in is used for P450 enzymes, which metabolize exogenous and endogenous compounds that include natural products, hormones, drugs, carcinogens. Feline leukemia virus subgroup C cellular receptor 1a (FLVCR1a) plasma membrane exporter ubiquitously expressed controls intracellular content hematopoietic lineages. We investigated role Flvcr1a function mice.We created mice with conditional disruption Mfsd7b,...
Feline leukemia virus subgroup C receptor 1 (Flvcr1) encodes two heme exporters: FLVCR1a, which localizes to the plasma membrane, and FLVCR1b, mitochondria. Here, we investigated role of Flvcr1 isoforms during erythropoiesis. We showed that, in mice zebrafish, Flvcr1a is required for expansion committed erythroid progenitors but cannot drive their terminal differentiation, while Flvcr1b contributes phase differentiation. FLVCR1a-down-regulated K562 cells have defective proliferation,...
Pain is necessary to alert us actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental mediate pain perception and humans without at permanent risk for injuries, burns mutilations. insensitivity can be caused by sensory neurodegeneration which a hallmark of hereditary autonomic neuropathies (HSANs). Although mutations several genes were previously associated with neurodegeneration, etiology many cases remains unknown. Using next...
Abstract The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is a transmembrane heme exporter essential for embryonic vascular development. However, the exact role of FLVCR1a during blood vessel development remains largely undefined. Here, we show that highly expressed in angiogenic endothelial cells (ECs) compared to quiescent ECs. Consistently, ECs lacking give rise structurally and functionally abnormal networks multiple models developmental pathologic angiogenesis. Firstly,...
Congenital insensitivity to pain (CIP) and hereditary sensory autonomic neuropathies (HSAN) are clinically genetically heterogeneous disorders exclusively or predominantly affecting the neurons. Due rarity of diseases findings based mainly on single case reports small series, knowledge about these is limited. Here, we describe molecular workup a large international cohort CIP/HSAN patients including from normally under-represented countries. We identify 80 previously unreported pathogenic...
Diamond-Blackfan anemia (DBA) is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations the upper limb or craniofacial region. Mutations in gene coding for ribosomal protein RPS19 have been identified 25% patients DBA, resulting impairment 18S rRNA processing and 40S subunit formation. Moreover, mutations genes account about DBA cases. Recently, analysis mice from which heme exporter...
Abstract The signaling cascade induced by the interaction of erythropoietin (EPO) with its receptor (EPO‐R) is a key event erythropoiesis. We present here data indicating that Fyn, Src‐family‐kinase, participates in EPO signaling‐pathway, since Fyn −/− mice exhibit reduced Tyr‐phosphorylation EPO‐R and decreased STAT5‐activity. importance erythropoiesis also supported blunted responsiveness to stress mouse erythroblasts adapt reactive oxygen species (ROS) activating...
Abstract Diamond–Blackfan anemia (DBA) is a congenital pure red cell aplasia often associated with skeletal malformations. Mutations in ribosomal protein coding genes, mainly RPS19, account for the majority of DBA cases. The molecular mechanisms underlying pathogenesis are still not completely understood. Alternative spliced isoforms FLVCR1 (feline leukemia virus subgroup C receptor 1) transcript non‐functional proteins have been reported some patients. Consistently, phenotype very close to...
FLVCR1 encodes for a ubiquitous heme exporter, whose recessive mutations cause posterior column ataxia with retinitis pigmentosa (PCARP). Recently, were also found in two sporadic children hereditary sensory‐autonomic neuropathy (HSAN). We report the unique case of 33‐year‐old Italian woman combination typical PCARP, sensory loss to all modalities and multiple autonomic dysfuctions, acute lymphocytic leukemia. Molecular analysis demonstrated homozygosity previously identified p.Pro221Ser...
Cardiomyopathy deeply affects quality of life and mortality patients with b-thalassemia or transfusion-dependent myelodysplastic syndromes. Recently, a link between Nrf2 activity iron metabolism has been reported in liver ironoverload murine models. Here, we studied C57B6 mice as healthy control nuclear erythroid factor-2 knockout (Nrf2-/-) male aged 4 12 months. Eleven-month-old wild-type Nrf2-/- were fed either standard diet containing 2.5% carbonyl-iron (iron overload [IO]) for weeks. We...
Abstract Hereditary sensory and autonomic neuropathies (HSANs) are a group of clinically genetically heterogeneous disorders the peripheral nervous system mainly characterized by impaired nociception dysfunction. We previously identified heme metabolism as novel pathway contributing to neurons maintenance nociception. Indeed, we reported mutations in feline leukemia virus subgroup C receptor 1 ( FLVCR1 ) gene individuals affected HSAN. encodes for 2 export proteins, FLVCR1a (plasma membrane)...
Cancer is one of the leading causes mortality worldwide. Beyond standard therapeutic options, whose effectiveness often reduced by drug resistance, repurposing antidiabetic metformin appears promising. Heme metabolism plays a pivotal role in control metabolic adaptations that sustain cancer cell proliferation. Recently, we demonstrated existence functional axis between heme synthetic enzyme ALAS1 and exporter FLVCR1a exploited cells to down-modulate oxidative metabolism. In colorectal lines,...