Preconditioning‐induced neuroprotection is mediated by reactive oxygen species and activation of the transcription factor nuclear factor‐κB
TLDR
The data suggest that inhibition of staurosporine‐induced neuronal apoptosis by preconditioning with xanthine/xanthine oxidase or FeSO4 involves an activation of NF‐κB and an increase in the protein level of Mn‐superoxide dismutase.Abstract:
Preconditioning by a sublethal stimulus induces tolerance to a subsequent, otherwise lethal insult and it has been suggested that reactive oxygen species (ROS) are involved in this phenomenon In the present study, we determined whether preconditioning activates the transcription factor nuclear factor-κB (NF-κB) and how this activation contributes to preconditioning-induced inhibition of neuronal apoptosis Preconditioning was performed by incubating mixed cultures of neurons and astrocytes from neonatal rat hippocampus with xanthine/xanthine oxidase or FeSO4 for 15 min followed by 24 h of recovery which protected the neurons against subsequent staurosporine-induced (200 nm, 24 h) apoptosis The cellular ROS content increased during preconditioning, but returned to basal levels after removal of xanthine/xanthine oxidase or FeSO4 We detected a transient activation of NF-κB 4 h after preconditioning as shown by immunocytochemistry, by a decrease in the protein level of IκBα as well as by electrophoretic mobility shift assay Preconditioning-mediated neuroprotection was abolished by antioxidants, inhibitors of NF-κB activation and cycloheximide suggesting the involvement of ROS, an activation of NF-κB and de novo protein synthesis in preconditioning-mediated rescue pathways Furthermore, preconditioning increased the protein level of Mn-superoxide dismutase which could be blocked by antioxidants, cycloheximide and κB decoy DNA Our data suggest that inhibition of staurosporine-induced neuronal apoptosis by preconditioning with xanthine/xanthine oxidase or FeSO4 involves an activation of NF-κB and an increase in the protein level of Mn-superoxide dismutaseread more
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Cerebral preconditioning and ischaemic tolerance
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Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
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