17 documents found, page 1 of 2
Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mo...
Simão, M.; Camacho, A.; Ostertag, A.; Cohen-Solal, M.; Pinto, I.; Porto, G.; Hang Korng, E.; Cancela, M.Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone l...
Genetic disruption of NRF2 promotes the development of necroinflammation and li...
Duarte, T.; Caldas, C.; Santos, A.; Silva-Gomes, S.; Santos-Gonçalves, A.; Martins, M.; Porto, G.; Lopes, J.In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepa...
Hepcidin is regulated by promoter-associated histone acetylation and HDAC3
Pasricha, S.; Lim, P.; Duarte, T.; Casu, C.; Oosterhuis, D.; Mleczko-Sanecka, K.; Suciu, M.; Da Silva, A.; Al-Hourani, K.; Arezes, J.; McHugh, K.Hepcidin regulates systemic iron homeostasis. Suppression of hepcidin expression occurs physiologically in iron deficiency and increased erythropoiesis but is pathologic in thalassemia and hemochromatosis. Here we show that epigenetic events govern hepcidin expression. Erythropoiesis and iron deficiency suppress hepcidin via erythroferrone-dependent and -independent mechanisms, respectively, in vivo, but both i...
Local iron homeostasis in the breast ductal carcinoma microenvironment
Marques, O.; Porto, G.; Rêma, A.; Faria, F.; Cruz Paula, A.; Gomez-Lazaro, M.; Silva, P.; Martins-Silva, B.; Lopes, C.Abstract BACKGROUND: While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. METHODS: Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to diss...
Lymphocyte gene expression signatures from patients and mouse models of heredit...
Costa, M.; Cruz, E.; Oliveira, S.; Benes, Vl.; Ivacevic, T.; Silva, M.; Vieira, I.; Dias, F.; Fonseca, S.; Gonçalves, M.; Lima, M.; Leitão, C.Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocyt...
Physiological implications of NTBI uptake by T lymphocytes
Pinto, J.; Arezes, J.; Dias, V.; Oliveira, S.; Vieira, I.; Costa, M.; Vos, M.; Carlsson, A.; Rikers, Y.; Rangel, M.; Porto, G.In iron overload disorders a significant fraction of the total iron circulates in the plasma as low molecular weight complexes not bound to transferrin, known as non-transferrin-bound iron (NTBI). By catalyzing the formation of free radicals, NTBI accumulation results in oxidative stress and cellular damage, being a major cause of organ toxicity. NTBI is rapidly and preferentially cleared from circulation by th...
Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigatin...
Bettencourt, B.F.; Rocha, F.L.; Alves, H.; Amorim, R.; Caetano Lopes, J.; Vieira Sousa, E.; Pimentel Santos, F.; Lima, M.; Porto, G.; Branco, J.C.OBJECTIVE: The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals. METHODS: A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were inv...
Effects of highly conserved major histocompatibility complex (MHC) extended hap...
Costa, M.; Cruz, E.; Barton, J.; Thorstensen, K.; Morais, S.; da Silva, B.; Pinto, J.; Vieira, C.; Vieira, J.; Acton, R.; Porto, G.Hereditary Hemochromatosis (HH) is a recessively inherited disorder of iron overload occurring commonly in subjects homozygous for the C282Y mutation in HFE gene localized on chromosome 6p21.3 in linkage disequilibrium with the human leukocyte antigen (HLA)-A locus. Although its genetic homogeneity, the phenotypic expression is variable suggesting the presence of modifying factors. One such genetic factor, a SN...
Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Sel...
Arezes, J.; Costa, M.; Vieira, I.; Dias, V.; Kong, X.; Fernandes, R.; Vos, M.; Carlsson, A.; Rikers, Y.; Porto, G.; Rangel, M.; Hider, R.; Pinto, J.Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible for the toxicit...
Alterações fenotípicas e genéticas do metabolismo do ferro numa população portu...
Crespo, A.C.; Silva, B.; Marques, L.; Marcelino, E.; Maruta, C.; Costa, S.; Timóteo, A.; Vilares, A.; Couto, F.S.; Faustino, Paula; Correia, A.P.