Rapid clearance of tertiary butyl hydroperoxide by cultured astroglial cells via oxidation of glutathione

Dringen, Ralf; Kußmaul, Lothar; Hamprecht, Bernd

doi:10.1002/(sici)1098-1136(199806)23:2<139::aid-glia5>3.0.co;2-1

Cited by 54 publications

(56 citation statements)

References 42 publications

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“…To examine whether elevated levels of endogenous H 2 O 2 might also affect DA cell physiology, we used MCS (Dringen et al, 1998) to inhibit glutathione (GSH) peroxidase, which should increase intracellular levels of H 2 O 2 by decreasing H 2 O 2 metabolism (Chen et al, 2002;. Changes in DCF fluorescence were used to indicate increases in H 2 O 2 in response to a range of MCS concentrations applied to a given cell (n ϭ 7).…”

Section: Effect Of Elevated Endogenous H 2 O 2 On Da Neurons Elevatiomentioning

confidence: 99%

Endogenous Hydrogen Peroxide Regulates the Excitability of Midbrain Dopamine Neurons via ATP-Sensitive Potassium Channels

Avshalumov¹,

Chen²,

Koós³

et al. 2005

J. Neurosci.

149

212

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ATP-sensitive K+(KATP) channels link metabolic state to cell excitability. Here, we examined regulation of KATPchannels in substantia nigra dopamine neurons by hydrogen peroxide (H2O2), which is produced in all cells during aerobic metabolism. Blockade of KATPchannels by glibenclamide (100 nm) or depletion of intracellular H2O2by including catalase, a peroxidase enzyme, in the patch pipette increased the spontaneous firing rate of all dopamine neurons tested in guinea pig midbrain slices. Using fluorescence imaging with dichlorofluorescein to visualize intracellular H2O2, we found that moderate increases in H2O2during partial inhibition of glutathione (GSH) peroxidase by mercaptosuccinate (0.1-0.3 mm) had no effect on dopamine neuron firing rate. However, with greater GSH inhibition (1 mmmercaptosuccinate) or application of exogenous H2O2, 50% of recorded cells showed KATPchannel-dependent hyperpolarization. Responsive cells also hyperpolarized with diazoxide, a selective opener for KATPchannels containing sulfonylurea receptor SUR1 subunits, but not with cromakalim, a selective opener for SUR2-based channels, indicating that SUR1-based KATPchannels conveyed enhanced sensitivity to elevated H2O2. In contrast, when endogenous H2O2levels were increased after inhibition of catalase, the predominant peroxidase in the substantia nigra, with 3-amino-1,2,4-triazole (1 mm), all dopamine neurons responded with glibenclamide-reversible hyperpolarization. Fluorescence imaging of H2O2indicated that catalase inhibition rapidly amplified intracellular H2O2, whereas inhibition of GSH peroxidase, a predominantly glial enzyme, caused a slower, smaller increase, especially in nonresponsive cells. Thus, endogenous H2O2modulates neuronal activity via KATPchannel opening, thereby enhancing the reciprocal relationship between metabolism and excitability.

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Section: Effect Of Elevated Endogenous H 2 O 2 On Da Neurons Elevatiomentioning

confidence: 99%

Endogenous Hydrogen Peroxide Regulates the Excitability of Midbrain Dopamine Neurons via ATP-Sensitive Potassium Channels

Avshalumov¹,

Chen²,

Koós³

et al. 2005

J. Neurosci.

149

212

View full text Add to dashboard Cite

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“…Allegedly, the mechanism of tBHP detoxification is based on the activity of glutathione peroxidase [23][24][25][26]. Therefore the meager effect of NAC on tBHP toxicity in our cell lines was unexpected.…”

Section: Discussionmentioning

confidence: 92%

“…In A549 cells, the NAC/NADC efficacy was tested also after additional 17 hours of exposure to tBHP. As tBHP (and other peroxides as well) were reported to feature half-life times of merely a few minutes [24], this 17-hour exposure period should provide sufficient time for cellular adaptation and recovery from the toxic burden. However, even in this setting no effect that could be attributed to glutathione synthesis was observed with the A549 cells in tBHP-mediated toxicity.…”

Section: Discussionmentioning

confidence: 99%

Glutathione Synthesis Against Oxidant Injury by Peroxides in Two Alveolar Epithelial Cell Lines

Walther

Mückter

2009

Experimental Lung Research

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The D- and L-forms of N-acetylcysteine (NADC, NAC) were tested in antagonizing the toxicity mediated by hydrogen peroxide (H(2)O(2)) or tertiary butyl hydroperoxide (tBHP) in two lung cell lines to assess the effectivity of glutathione synthesis against peroxides. Toxicity was assessed by methionine incorporation, total glutathione content, and glutathione disulfide to glutathione ratio. NAC or NADC, at 2 mmol/L, increased cellular glutathione to about 1.5- or 3-fold (NAC) and 1.1- or 1.2-fold (NADC) in A549 or L2 cells, respectively, as compared to naive cells. H(2)O(2)-mediated toxicity was decreased by NADC (as compared to controls), but increased slightly with NAC, whereas tBHP-mediated toxicity was decreased both by NAC and NADC. However, when compared to controls, NADC was an effective antidote against tBHP in L2 cells only. Dexamethasone pretreatment increased toxicity of H(2)O(2) and tBHP in L2 cells, but did not affect the antioxidative efficacy of NAC/NADC. Antidotal properties of NAC/NADC were similar in both cell lines, despite significant differences of the glutathione redox system in both situations. Hence, it is concluded that direct antioxidative properties of NAC and NADC is a main antagonizing factor in H(2)O(2)-based toxicity but not in tBHP-mediated toxicity. Enhancement of glutathione biosynthesis decreased toxicity of tBHP, but not of H(2)O(2) in 2 pulmonary cell lines.

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“…On the other hand incubation periods in L2 cells were the same for tBHP and HP. Dringen et al (1998) has demonstrated, that the half life time of tBHP in medium (even without cells) is in the range of about 15 min (or shorter). Therefore exposure of cells towards the peroxides can be described as independent from exposure periods, if these are longer than approximately 1 h (about 4-5 t/2).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid pretreatment increases toxicity due to peroxides in alveolar epithelial-like cell lines

Walther¹,

Stets²

2009

Toxicology

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Rapid clearance of tertiary butyl hydroperoxide by cultured astroglial cells via oxidation of glutathione

Cited by 54 publications

References 42 publications

Endogenous Hydrogen Peroxide Regulates the Excitability of Midbrain Dopamine Neurons via ATP-Sensitive Potassium Channels

Endogenous Hydrogen Peroxide Regulates the Excitability of Midbrain Dopamine Neurons via ATP-Sensitive Potassium Channels

Glutathione Synthesis Against Oxidant Injury by Peroxides in Two Alveolar Epithelial Cell Lines

Glucocorticoid pretreatment increases toxicity due to peroxides in alveolar epithelial-like cell lines

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