7 documents found, page 1 of 1
Targeting circulating labile heme as a defense strategy against malaria
Ramos, Susana; Jeney, Viktoria; Figueiredo, Ana; Paixão, Tiago; Sambo, Maria Rosário; Quinhentos, Vatúsia; Martins, Rui; Gouveia, ZéliaSevere presentations of malaria emerge as Plasmodium (P.) spp. parasites invade and lyse red blood cells (RBC), producing extracellular hemoglobin (HB), from which labile heme is released. Here, we tested whether scavenging of extracellular HB and/or labile heme, by haptoglobin (HP) and/or hemopexin (HPX), respectively, counter the pathogenesis of severe presentations of malaria. We found that circulating labil...
Ferritin heavy chain supports stability and function of the regulatory T cell l...
Wu, Qian; Carlos, Ana Rita; Braza, Faouzi; Bergman, Marie-Louise; Kitoko, Jamil Z; Bastos-Amador, Patricia; Cuadrado, Eloy; Martins, RuiRegulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten–eleven transl...
DNA damage independent inhibition of NF-κB transcription by anthracyclines
Pedroso, Dora; Chora, Ângelo Ferreira; Kyriakou, Eleni; Pejanovic, Nadja; Colaço, Henrique; Gozzelino, Raffaella; Barros, André; Willmann, KatharinaAnthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here, we show that the extensively used anthracyclines Doxorubicin, Daunorubicin, and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targ...
Red alert: labile heme is an alarmin
Soares, Miguel P; Bozza, Marcelo TAlarmins are a heterogeneous group of endogenous molecules that signal cellular damage when sensed extracellularly. Heme is an endogenous molecule that acts as a prosthetic group of hemoproteins, such as hemoglobin and myoglobin. When released from damaged red blood cells or muscle cells, oxidized hemoglobin and myoglobin release their prosthetic heme groups, respectively. This generates labile heme, which is s...
Disruption of Parasite hmgb2 Gene Attenuates Plasmodium berghei ANKA Pathogenicity
Briquet, Sylvie; Lawson-Hogban, Nadou; Boisson, Bertrand; Soares, Miguel P; Péronet, Roger; Smith, Leanna; Ménard, Robert; Huerre, MichelEukaryotic high-mobility-group-box (HMGB) proteins are nuclear factors involved in chromatin remodeling and transcription regulation. When released into the extracellular milieu, HMGB1 acts as a proinflammatory cytokine that plays a central role in the pathogenesis of several immune-mediated inflammatory diseases. We found that the Plasmodium genome encodes two genuine HMGB factors, Plasmodium HMGB1 and HMGB2, ...
Macrophages sense and kill bacteria through carbon monoxide-dependent inflammas...
Wegiel, Barbara; Larsen, Rasmus; Gallo, David; Chin, Beek Yoke; Harris, Clair; Mannam, Praveen; Kaczmarek, Elzbieta; Lee, Patty J; Zuckerbraun, Brian SMicrobial clearance by eukaryotes relies on complex and coordinated processes that remain poorly understood. The gasotransmitter carbon monoxide (CO) is generated by the stress-responsive enzyme heme oxygenase-1 (HO-1, encoded by Hmox1), which is highly induced in macrophages in response to bacterial infection. HO-1 deficiency results in inadequate pathogen clearance, exaggerated tissue damage, and increased mo...
Tissue damage control in disease tolerance
Soares, Miguel P; Gozzelino, Raffaella; Weis, SebastianImmune-driven resistance mechanisms are the prevailing host defense strategy against infection. By contrast, disease tolerance mechanisms limit disease severity by preventing tissue damage or ameliorating tissue function without interfering with pathogen load. We propose here that tissue damage control underlies many of the protective effects of disease tolerance. We explore the mechanisms of cellular adaptatio...