Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors.
Blood
; 127(1): 139-48, 2016 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-26463424
ABSTRACT
Maintaining cellular redox balance is vital for cell survival and tissue homoeostasis because imbalanced production of reactive oxygen species (ROS) may lead to oxidative stress and cell death. The antioxidant enzyme glutathione peroxidase 4 (Gpx4) is a key regulator of oxidative stress-induced cell death. We show that mice with deletion of Gpx4 in hematopoietic cells develop anemia and that Gpx4 is essential for preventing receptor-interacting protein 3 (RIP3)-dependent necroptosis in erythroid precursor cells. Absence of Gpx4 leads to functional inactivation of caspase 8 by glutathionylation, resulting in necroptosis, which occurs independently of tumor necrosis factor α activation. Although genetic ablation of Rip3 normalizes reticulocyte maturation and prevents anemia, ROS accumulation and lipid peroxidation in Gpx4-deficient cells remain high. Our results demonstrate that ROS and lipid hydroperoxides function as not-yet-recognized unconventional upstream signaling activators of RIP3-dependent necroptosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Estresse Oxidativo
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Células Eritroides
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Proteína Serina-Treonina Quinases de Interação com Receptores
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Glutationa Peroxidase
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Necrose
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2016
Tipo de documento:
Article