Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-lpr mice.
Lupus Sci Med
; 7(1)2020 04.
Article
em En
| MEDLINE
| ID: mdl-32343673
ABSTRACT
OBJECTIVES:
Recent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells from patients with lupus, the increased mROS is capable of provoking oligomerisation of mitochondrial antiviral stimulator (MAVS) and production of type I interferon (IFN-I). mROS in SLE neutrophils also promotes the formation of neutrophil extracellular traps (NETs), which are increased in lupus and implicated in renal damage. As a result, in addition to traditional immunosuppression, more comprehensive treatments for lupus may also include non-immune therapy, such as antioxidants.METHODS:
Lupus-prone MRL-lpr mice were treated from weaning for 11 weeks with the mitochondria-targeted antioxidant, MitoQ (200 µM) in drinking water. Mice were then assessed for ROS production in neutrophils, NET formation, MAVS oligomerisation, serum IFN-I, autoantibody production and renal function.RESULTS:
MitoQ-treated mice manifested reduced neutrophil ROS and NET formation, decreased MAVS oligomerisation and serum IFN-I, and reduced immune complex formation in kidneys, despite no change in serum autoantibody .CONCLUSIONS:
These findings reveal the potential utility of targeting mROS in addition to traditional immunosuppressive therapy for lupus.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
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Ubiquinona
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Armadilhas Extracelulares
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Nefropatias
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Lúpus Eritematoso Sistêmico
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Mitocôndrias
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article