The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation
Open accessAbstract
When activated by proinflammatory stimuli, microglia release substantial levels of glutamate, and mounting evidence suggests this contributes to neuronal damage during neuroinflammation. Prior studies indicated a role for the Xc exchange system, an amino acid transporter that antiports glutamate for cystine. Because cystine is used for synthesis of glutathione (GSH) synthesis, we hypothesized that glutamate release is an indirect consequence of GSH depletion by the respiratory burst, which produces superoxide from NADPH oxidase. Microglial glutamate release triggered by lipopolysaccharide was blocked by diphenylene iodonium chloride and apocynin, inhibitors of NADPH oxidase. This glutamate release was also blocked by vitamin E and elicited by lipid peroxidation products 4‐hydroxynonenal and acrolein, suggesting that lipid peroxidation makes crucial demands on GSH. Although NADPH oxidase inhibitors also suppressed nitrite accumulation, vitamin E did not; moreover, glutamate release was largely unaffected by nitric oxide donors, inhibitors of nitric oxide synthase, or changes in gene expression. These findings indicate that a considerable degree of the neurodegenerative consequences of neuroinflammation may result from conversion of oxidative stress to excitotoxic stress. This phenomenon entails a biochemical chain of events initiated by a programmed oxidative stress and resultant mass‐action amino acid transport. Indeed, some of the neuroprotective effects of antioxidants may be due to interference with these events rather than direct protection against neuronal oxidation.
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Cites
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Cited by
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
The role of inflammation in perinatal brain injury
Hagberg, H., Mallard, C., Ferriero, D. M., Vannucci, S. J., Levison, S. W., Vexler, Z. S., & Gressens, P. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.13 · Cited by 829
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594
Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
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Metadata
- Authors
- Barger, S. W., Goodwin, M. E., Porter, M. M., & Beggs, M. L.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-02-20
- Volume
- 101
- Issue
- 5
- Pages
- 1205-1213
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2093412414
- Cited by
- 254
- References
- 46
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- bronze
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