Glutathione peroxidase 4 (GPx4) is the only enzyme capable of reducing toxic lipid hydroperoxides in biological membranes to the corresponding alcohols using glutathione as the electron donor. GPx4 is the major inhibitor of ferroptosis, a non-apoptotic and iron-dependent programmed cell death pathway, which has been shown to occur in various neurological disorders with severe oxidative stress. In this study, we investigate whether GPx4 expression is altered in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). The results clearly show that mRNA expression for all three GPx4 isoforms (cytoplasmic, mitochondrial and nuclear) decline in multiple sclerosis gray matter and in the spinal cord of MOG35-55 peptide-induced EAE. The amount of GPx4 protein is also reduced in EAE, albeit not in all cells. Neuronal GPx4 immunostaining, mostly cytoplasmic, is lower in EAE spinal cords than in control spinal cords, while oligodendrocyte GPx4 immunostaining, mainly nuclear, is unaltered. Neither control nor EAE astrocytes and microglia cells show GPx4 labeling. In addition to GPx4, two other negative modulators of ferroptosis (γ-glutamylcysteine ligase and cysteine/glutamate antiporter), which are critical to maintain physiological levels of glutathione, are diminished in EAE. The decrease in the ability to eliminate hydroperoxides was also evidenced by the accumulation of lipid peroxidation products and the reduction in the proportion of the docosahexaenoic acid in non-myelin lipids. These findings, along with presence of abnormal neuronal mitochondria morphology, which includes an irregular matrix, disrupted outer membrane and reduced/absent cristae, are consistent with the occurrence of ferroptotic damage in inflammatory demyelinating disorders.
Pubmed ID: 30289974 RIS Download
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This monoclonal targets Car2
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View all literature mentionsThis monoclonal targets Glutathione Peroxidase 4
View all literature mentionsThis monoclonal targets Glutathione Peroxidase 4 antibody [EPNCIR144]
View all literature mentionsThis polyclonal targets xCT antibody
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View all literature mentionsThis polyclonal targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets Glutathione Peroxidase 4 antibody [EPNCIR144]
View all literature mentionsThis monoclonal targets Car2
View all literature mentionsThis polyclonal targets IgG (H + L)
View all literature mentionsThis polyclonal targets xCT antibody
View all literature mentionsThis monoclonal targets GAPDH (6C5)
View all literature mentionsThis monoclonal targets Glutathione Peroxidase 4
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal targets Goat IgG
View all literature mentionsThis monoclonal targets GFAP
View all literature mentions