The relative roles of the glutathione redox cycle and catalase in the detoxification of H2O2 by cultured rabbit lens epithelial cells

Giblin, Frank J.; Reddan, John R.; Schrimscher, Lisa; Dziedzic, Dorothy C.; Reddy, Venkat N.

doi:10.1016/0014-4835(90)90130-m

Cited by 67 publications

(26 citation statements)

References 32 publications

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“…This is an opposite finding to prior studies where treatment of cells with higher concentrations of H 2 O 2 also induced higher catalase activity (Cantoni et al, 1993 (Giblin et al, 1990). Giblin et al suggested that the function of the glutathione system mainly lies in the detoxification of secondary peroxidation products and is therefore vital for cell survival.…”

Section: Discussioncontrasting

confidence: 55%

Generation of hydrogen peroxide-resistant murine neuroblastoma cells: a target discovery platform for novel neuroprotective genes

et al. 2013

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Oxidative stress has been suggested to play an important role in the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Hydrogen peroxide (H2O2), one of the main reactive oxygen species, is converted into the highly toxic ·OH radical in the presence of redox-active transition metals, which then oxidises nucleic acids, lipids and proteins, leading to neurodegeneration and cell death. There is an urgent need to gain more knowledge about relevant therapeutic targets to combat oxidative stress and it neurotoxic effects, and how this knowledge can be utilized to develop novel neuroprotective therapies for AD. One way to identify new mechanisms combating oxidative stress was via the creation of H2O2-resistant cell lines and identification of the mechanisms responsible for their resistance. However, in most cases catalase overexpression or increased glutathione content was identified as the primary mode of H2O2 resistance in these cell lines. In this study, we have generated six different resistant neuronal cell lines or populations (from the same original murine Neuro2a neuroblastoma line) by exposing cells to increasing concentrations of H2O2 and performing continuous selection for survivors over a period of several months, which appear to have acquired H2O2 resistance based on other, novel mechanisms. These six populations showed a significant, but differential resistance against H2O2 when compared with the parental cell line. Using combinations of catalase-, glutathione synthesis-and glutathione peroxidase-inhibitors it was shown that the increased resistance of Neuro2a-HR cells is not solely based on an increased activity of catalase or the glutathione system, suggesting that their resistance might be based on yet unknown, novel defence mechanisms.

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Section: Discussioncontrasting

confidence: 55%

Generation of hydrogen peroxide-resistant murine neuroblastoma cells: a target discovery platform for novel neuroprotective genes

et al. 2013

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“…The level of GSH decreased 46% after 5 min of treatment with 0.1 mM H 2 O 2 , but by 15 min of treatment, the levels of GSH returned to the pretreatment level and remained constant thereafter. The rapid restitution of GSH confirms that BLEC have an active system to restore intracellular redox status (42) and that this protective apparatus is not permanently altered by the H 2 O 2 exposure. These data also indicate that cells treated with 0.1 mM H 2 O 2 need less time to restore the intracellular level of GSH than the cells treated with 1 mM H 2 O 2 , since the level of intracellular GSH in the cells treated with 1 mM H 2 O 2 was still 50% lower after 15 min of treatment (19).…”

Section: Changes Of Redox Status and Atp Levels In Blec Uponmentioning

confidence: 74%

“…To assess the effect of this level of H 2 O 2 on cultured BLEC, the levels of reduced glutathione (GSH), an indicator of cellular redox status (42), were determined during and after H 2 O 2 treatment. The level of GSH decreased 46% after 5 min of treatment with 0.1 mM H 2 O 2 , but by 15 min of treatment, the levels of GSH returned to the pretreatment level and remained constant thereafter.…”

Section: Changes Of Redox Status and Atp Levels In Blec Uponmentioning

confidence: 99%

Activity of Ubiquitin-dependent Pathway in Response to Oxidative Stress

Shang

Gong

Taylor

1997

Journal of Biological Chemistry

215

135

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Relations between the ubiquitin pathway and cellular stress have been noted, but data regarding responses of the ubiquitin pathway to oxidative stress are scanty. This paper documents the response of this pathway to oxidative stress in lens cells. A brief exposure of lens epithelial cells to physiologically relevant levels of H 2 O 2 induces a transient increase in activity of the ubiquitindependent pathway. Ubiquitin conjugation activity was maximal and increased 3.5-9.2-fold over the activity noted in untreated cells by 4 h after removal of H 2 O 2 . By 24 h after removal of H 2 O 2 , ubiquitin conjugation activity returned to the level noted in untreated cells. In parallel to the changes in ubiquitin conjugation activity, the activity of ubiquitin-activating enzyme (E1), as determined by thiol ester formation, increased 2-6.7-fold during recovery from oxidation. Addition of exogenous E1 resulted in an increase in ubiquitin conjugation activity and in the levels of ubiquitin carrier protein (E2)-ubiquitin thiol esters in both the untreated cells and the H 2 O 2 -treated cells. These data suggest that E1 is the rate-limiting enzyme in the ubiquitin conjugation process and that the increases in ubiquitin conjugation activity which are induced upon recovery from oxidation are primarily due to increased E1 activity. The oxidation-and recovery-induced up-regulation of E1 activity is primarily due to post-synthetic events. Substrate availability and up-regulation of E2 activities also appear to be related to the enhancement in ubiquitinylation upon recovery from oxidative stress. The oxidationinduced increases in ubiquitin conjugation activity were associated with an increase in intracellular proteolysis, suggesting that the transient increase in ubiquitinylation noted upon recovery from oxidative stress may play a role in removal of damaged proteins from the cells.

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“…25,[27][28][29], In rabbit lens epithelial cells. Giblin et al [11] noted that for cells treated with a low (25 \iM) steady-state level of H20 2, the glutathione redox cycle was the primary means ofdefense against oxidative damage. Cells with fully active catalase but inhibited glutathione reductase were not able to resist the cytotoxic effects o f a 25 \\M level of extra cellular peroxide.…”

Section: Discussionmentioning

confidence: 99%

Peroxide-Induced Damage in Lenses of Transgenic Mice with Deficient and Elevated Levels of Glutathione Peroxidase

Reddy

Lin

et al. 1997

Ophthalmologica

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Transgenic mice with elevated glutathione peroxidase (GSHPx) activity and gene knockout animals with a deficiency of the enzyme were used to investigate the role of GSHPx in defending the lens against H₂O₂-induced damage. The effects of peroxide on cultured lenses were determined by using light and transmission electron microscopy to evaluate morphological changes occurring in the epithelium and superficial cortex of the central and equatorial regions of the lens. DNA single-strand breaks in the epithelium were also examined. Following a 30-min exposure to 25 µM H₂O₂, lenses from normal animals showed distinct changes in the morphology of both the epithelium and superficial cortex. The damage to these cells was extensive in lenses of gene knockout mice in which activity of GSHPx was undetectable. In marked contrast, lenses of transgenic mice, which had 5-fold higher activities of GSHPx, were able to resist the cyto-toxic effects. Similar to damage to cell morphology, the extent of DNA strand breaks was significantly lower (40% of control) in H₂O₂-exposed lenses as compared to normal lenses while DNA damage in gene knockout lenses was 5 times greater than that of GSHPx-rich transgenic lenses. The present studies extend our previous findings on the role of the glutathione redox cycle in the detoxification of peroxide and demonstrate that an increase in GSHPx activity protects the lens against peroxide-induced changes in cell morphology and DNA strand breaks.

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The relative roles of the glutathione redox cycle and catalase in the detoxification of H2O2 by cultured rabbit lens epithelial cells

Cited by 67 publications

References 32 publications

Generation of hydrogen peroxide-resistant murine neuroblastoma cells: a target discovery platform for novel neuroprotective genes

Generation of hydrogen peroxide-resistant murine neuroblastoma cells: a target discovery platform for novel neuroprotective genes

Activity of Ubiquitin-dependent Pathway in Response to Oxidative Stress

Peroxide-Induced Damage in Lenses of Transgenic Mice with Deficient and Elevated Levels of Glutathione Peroxidase

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