The involvement of nuclear factor-κB in astroprotection against ischemia-reperfusion injury by ischemia-preconditioned neurons.
Ischemic preconditioned (IP) neurons protect astrocytes against ischemia/reperfusion (I/R)-induced injury by inhibiting oxidative stress. However, the relevant mechanisms are unknown. Based on the role of nuclear factor-κB (NF-κB) in cell survival and adaption to oxidative stress, we hypothesized that NF-κB might be associated with astroprotection induced by IP neurons via upregulation of antioxidant enzymes. Here, we investigated the effects of IP neurons on NF-κB activation, cell viability, reactive oxygen species (ROS), expression of antioxidant enzymes, erythropoietin (EPO), and tumor necrosis factor α (TNF-α), in the presence or absence of BAY11-7082 (an NF-κB inhibitor), anti-EPO, and anti-TNF-α antibodies, in astrocytes treated with or without I/R. We found that IP neurons could keep NF-κB activation at a relatively higher but beneficial level, and in turn, upregulated the activity of antioxidant enzymes and hence enhanced cell viability and reduced ROS in I/R treated astrocytes. The results collectively indicated that IP neurons are able to significantly inhibit the I/R-induced NF-κB overactivation, probably via EPO and TNF-α, being essential for IP neuron-induced astroprotection under the conditions of I/R. We concluded that NF-κB-mediated antioxidative stress is one of the mechanisms by which IP neurons protect astrocytes against I/R injury.
['Wu|Xiao-Mei|XM|', 'Qian|Christopher|C|', 'Jiang|Fei|F|', 'Bao|Yu-Xin|YX|', 'Qian|Zhong-Ming|ZM|0000-0001-7851-0455', 'Ke|Ya|Y|']
D000818:Animals D000975:Antioxidants D001253:Astrocytes D015687:Cell Hypoxia D002478:Cells, Cultured D002540:Cerebral Cortex D017077:Culture Media, Conditioned D004921:Erythropoietin D005947:Glucose D016328:NF-kappa B D009474:Neurons D018384:Oxidative Stress D019899:Paracrine Communication D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D015427:Reperfusion Injury D015398:Signal Transduction D014409:Tumor Necrosis Factor-alpha
astroprotection antioxidation enzymes reactive oxygen species (ROS) ischemia-preconditioned neuron culture medium (IPcNCM) ischemia/reperfusion (I/R) nuclear factor κB (NF-κB)