Nox4-dependent H2O2 production contributes to chronic glutamate toxicity in primary cortical neurons

Astrocytic phospholipase A2 contributes to neuronal glutamate toxicity

“…Chronic toxicity is associated with the production of extracellular H 2 O 2 , which is dependent on NADPH oxidase (Nox) expression (Ha et al, 2010). Here, we show that neuronal sensitivity to chronic glutamate exposure, but not acute exposure, is increased in the presence of astrocytes.…”

“…Chronic glutamate toxicity in co-cultures is not dependent on extracellular H 2 O 2 Chronic glutamate toxicity in pure neuron cultures depends on Nox4 expression (Ha et al, 2010). Nox4-derived extracellular rather than intracellular H 2 O 2 largely contributes to neuronal cytotoxicity in chronic glutamate exposure.…”

“…However, neurotoxicity through chronic glutamate exposure (chronic toxicity) has been considered a slow variant of excitotoxicity (acute toxicity) because of their similar sensitivities to glutamate and receptor-specific agonists. Recently, chronic toxicity has been distinguished from acute toxicity based on extracellular H 2 O 2 generation in pure cultures of mature primary neurons (Ha et al, 2010).…”

Anti-heat Shock 70 kDa Protein Antibody Induced Neuronal Cell Death

“…Reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has been reported to be involved in the generation of hydrogen peroxide in primary cortical neurons. 40) However, NADPH oxidase inhibitors (apocynin, diphenylene iodonium and VAS2870) could not prevent neurons from undergoing the anti-Hsp70 antibody-induced hydrogen peroxide generation and cell death (data not shown). The neuroprotective effect of other inhibitors of hydrogen peroxide-generating enzymes including monoamine oxidase B and xanthine oxidase could not be detected (data not shown).…”

Paracrine Neuroprotective Effects of Neural Stem Cells on Glutamate-Induced Cortical Neuronal Cell Excitotoxicity

“…Furthermore, the cystine uptake is inhibited which decreases intracellular glutathione levels and finally lead to neuronal oxidative stress. 6 Glutamate-induced excitotoxicity has been reported in both acute injuries such as ischemic stroke, and chronic brain disorders such as Alzheimer's and Parkinson's diseases. 2 Studies showed that glutamate receptors antagonists are not efficient to protect neurons against excitotoxicity and hence it is necessary to find new approaches to limiting glutamate-induced toxicity.…”