Autor | Mittra, Bidyottam | |
Autor | Silva, Maria Fernanda Laranjeira | |
Autor | Miguel, Danilo Ciccone | |
Autor | Menezes, Juliana Perrone Bezerra de | |
Autor | Andrews, Norma W | |
Data de acesso | 2018-03-26T14:34:09Z | |
Data de disponibilização | 2018-03-26T14:34:09Z | |
Data do publicação | 2017 | |
Citação | MITTRA, B. et al. The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence. Journal of Biological Chemistry, v. 292, n. 29, p. 12324–12338, 2017. | pt_BR |
ISSN | 0021-9258 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/25492 | |
Descrição | Menezes, Juliana Perrone Bezerra de. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. | pt_BR |
Fomento | National Institutes of Health Grant R01 AI067979 (to N. W. A.). | pt_BR |
Idioma | eng | pt_BR |
Editor | American Society for Biochemistry and Molecular Biology | pt_BR |
Direito Autoral | open access | pt_BR |
Palavras-chave | Leishmania | pt_BR |
Palavras-chave | Diferenciação | pt_BR |
Palavras-chave | Ferro superóxido dismutase | pt_BR |
Palavras-chave | Mitocôndria | pt_BR |
Palavras-chave | Sinalização redox | pt_BR |
Palavras-chave | Superóxido dismutase (SOD | pt_BR |
Título | The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence | pt_BR |
Tipo do documento | Article | pt_BR |
DOI | 10.1074/jbc.M116.772624 | |
Resumo em Inglês | Leishmaniasis is one of the leading globally neglected diseases, affecting millions of people worldwide.Leishmaniainfection depends on the ability of insect-transmitted metacyclic promastigotes to invade mammalian hosts, differentiate into amastigotes, and replicate inside macrophages. To counter the hostile oxidative environment inside macrophages, these protozoans contain anti-oxidant systems that include iron-dependent superoxide dismutases (SODs) in mitochondria and glycosomes. Increasing evidence suggests that in addition to this protective role,Leishmaniamitochondrial SOD may also initiate H2O2-mediated redox signaling that regulates gene expression and metabolic changes associated with differentiation into virulent forms. To investigate this hypothesis, we examined the specific role of SODA, the mitochondrial SOD isoform inLeishmania amazonensisOur inability to generateL. amazonensis SODAnull mutants and the lethal phenotype observed following RNAi-mediated silencing of theTrypanosoma brucei SODAortholog suggests that SODA is essential for trypanosomatid survival.L. amazonensismetacyclic promastigotes lacking oneSODAallele failed to replicate in macrophages and were severely attenuated in their ability to generate cutaneous lesions in mice. Reduced expression of SODA also resulted in mitochondrial oxidative damage and failure ofSODA/ΔsodApromastigotes to differentiate into axenic amastigotes. SODA expression above a critical threshold was also required for the development of metacyclic promastigotes, asSODA/ΔsodAcultures were strongly depleted in this infective form and more susceptible to reactive oxygen species (ROS)-induced stress. Collectively, our data suggest that SODA promotesLeishmaniavirulence by protecting the parasites against mitochondrion-generated oxidative stress and by initiating ROS-mediated signaling mechanisms required for the differentiation of infective forms. | pt_BR |
Afiliação | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA | pt_BR |
Afiliação | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA | pt_BR |
Afiliação | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA | pt_BR |
Afiliação | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA | pt_BR |
Afiliação | University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USA | pt_BR |
Palavras-chave em inglês | Leishmania | pt_BR |
Palavras-chave em inglês | Differentiation | pt_BR |
Palavras-chave em inglês | Iron superoxide dismutase | pt_BR |
Palavras-chave em inglês | Mitochondria | pt_BR |
Palavras-chave em inglês | Redox signaling | pt_BR |
Palavras-chave em inglês | Superoxide dismutase (SOD) | pt_BR |