Extracellular hydrogen peroxide contributes to oxidative glutamate toxicity

Ha, Jong Seong; Lim, Heon M.; Park, Sung Sup

doi:10.1016/j.brainres.2010.08.086

Cited by 37 publications

(34 citation statements)

References 36 publications

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“…Accumulation of oxidants or overconsumption of antioxidants will damage cellular metabolism and even result in cell death [27]. In this study, we found that when in conditions of oxidative stress AEA raised intracellular SOD and GSH, reduced GSSG, and increased the GSH/GSSG ratio, and these effects were reversed by CB1 antagonist AM251, indicating that AEA could restore the balance of intracellular antioxidative and oxidative substances via CB1 receptor.…”

Section: Discussionmentioning

confidence: 55%

Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase

Jia

et al. 2014

Oxidative Medicine and Cellular Longevity

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Background. Endogenous cannabinoid anandamide (AEA) protects neurons from oxidative injury in rodent models; however the mechanism of AEA-induced neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2 (Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can attenuate cerebral oxidative stress. We aimed to determine whether the neuronal Nox2 was involved in protection mediated by AEA. Methods. The mouse hippocampal neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative injury of neurons. The protective effect of AEA was assessed by measuring cell metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular morphology, intracellular reactive oxygen species (ROS), and antioxidant and oxidant levels and Nox2 expression. Results. HT22 cells exposed to H2O2 demonstrated morphological changes, decreased LDH release, reduced metabolic activity, increased levels of intracellular ROS and oxidized glutathione (GSSG), reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and increased expression of Nox2. AEA prevented these effects, a property abolished by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA. Conclusion. Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative stress through CB1 activation in HT22 cells.

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Section: Discussionmentioning

confidence: 55%

Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase

Jia

et al. 2014

Oxidative Medicine and Cellular Longevity

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“…NOX2 deletion or DPI mitigates NOX activity, ROS production, and apoptotic death triggered by staurosporine in these cells, which suggests an important role of NOX2 in apoptotic death of neurons [42, 43]. Knockdown of NOX2 and NOX4 expression in cultured HT22 neuronal cells reduces glutamate-induced hydrogen peroxide accumulation and cell death, indicating NOX family contributes to oxidative glutamate toxicity [44]. NOX4 is upregulated in human and mouse brain after ischemia; post -stroke inhibition of NOX4 induction in mice prevents oxidative stress and neurodegeneration [45].…”

Section: Nox Is An Important Source Of Cns Oxidative Stressmentioning

confidence: 99%

NADPH oxidases: novel therapeutic targets for neurodegenerative diseases

Gao

Zhou

Hong

2012

Trends in Pharmacological Sciences

189

156

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Oxidative stress is a key pathologic factor in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a major superoxide-producing enzyme complex in activated phagocytes, phagocytic NADPH oxidase (PHOX) is essential for host defense. However, recent preclinical evidence has underscored a pivotal role of over-activated PHOX in chronic neuroinflammation and progressive neurodegeneration. Deficiency in PHOX subunits mitigates neuronal damage induced by diverse insults/stresses relevant to neurodegenerative diseases. More importantly, the suppression of PHOX activity correlates with less neuronal impairment in models of neurodegenerative diseases. The discovery of PHOX and non-phagocytic NADPH oxidases in astroglia and neurons further reinforces the critical role of NADPH oxidases in oxidative stress-mediated chronic neurodegeneration. Thus, proper modulation of NADPH oxidase activity might hold therapeutic potential for currently incurable neurodegenerative diseases.

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“…There are studies indicating that NOX4 may produce H 2 O 2 directly instead of superoxide (16,77). However, a number of studies (26,31,59,68) indicate that NOX4 first produces O 2…”

Section: We Hypothesized That Ang II Stimulates Omentioning

confidence: 99%

Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4

Massey

Hong

Garvin

2012

American Journal of Physiology-Cell Physiology

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Angiotensin II (ANG II) stimulates production of superoxide (O(2)(-)) by NADPH oxidase (NOX) in medullary thick ascending limbs (TALs). There are three isoforms of the catalytic subunit (NOX1, 2, and 4) known to be expressed in the kidney. We hypothesized that NOX2 mediates ANG II-induced O(2)(-) production by TALs. To test this, we measured NOX1, 2, and 4 mRNA and protein by RT-PCR and Western blot in TAL suspensions from rats and found three catalytic subunits expressed in the TAL. We measured O(2)(-) production using a lucigenin-based assay. To assess the contribution of NOX2, we measured ANG II-induced O(2)(-) production in wild-type and NOX2 knockout mice (KO). ANG II increased O(2)(-) production by 346 relative light units (RLU)/mg protein in the wild-type mice (n = 9; P < 0.0007 vs. control). In the knockout mice, ANG II increased O(2)(-) production by 290 RLU/mg protein (n = 9; P < 0.007 vs. control). This suggests that NOX2 does not contribute to ANG II-induced O(2)(-) production (P < 0.6 WT vs. KO). To test whether NOX4 mediates the effect of ANG II, we selectively decreased NOX4 expression in rats using an adenovirus that expresses NOX4 short hairpin (sh)RNA. Six to seven days after in vivo transduction of the kidney outer medulla, NOX4 mRNA was reduced by 77%, while NOX1 and NOX2 mRNA was unaffected. In control TALs, ANG II stimulated O(2)(-) production by 96%. In TALs transduced with NOX4 shRNA, ANG II-stimulated O(2)(-) production was not significantly different from the baseline. We concluded that NOX4 is the main catalytic isoform of NADPH oxidase that contributes to ANG II-stimulated O(2)(-) production by TALs.

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Extracellular hydrogen peroxide contributes to oxidative glutamate toxicity

Cited by 37 publications

References 36 publications

Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase

Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase

NADPH oxidases: novel therapeutic targets for neurodegenerative diseases

Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4

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