API

Event: 926

Key Event Title

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Oxidation, Glutathione (To be considered with MIE)

Short name

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Oxidation, Glutathione

Key Event Component

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Process Object Action
antioxidant activity glutathione abnormal

Key Event Overview


AOPs Including This Key Event

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Stressors

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Level of Biological Organization

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Biological Organization
Molecular

Cell term

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Organ term

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens Strong NCBI
Bos taurus Bos taurus Strong NCBI
Mus musculus Mus musculus Strong NCBI
Rattus norvegicus Rattus norvegicus Strong NCBI

Life Stage Applicability

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Life stage Evidence
All life stages Strong

Sex Applicability

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Term Evidence
Unspecific Strong

How This Key Event Works

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**NOTE** : This KE has been revised to be part of the MIE; Peptide Oxidation.

 

Glutathione (GSH) oxidation refers to the conversion of reduced glutathione to its oxidized form glutathione disulfide (GSSG) in the presence of oxidative species. GSH plays an important role as an anti-oxidant in regulating cellular redox homeostasis, and is mainly present in the cell as the reduced form (98%). Deficiency in GSH or a decrease in GSH/GSSG ratio results in decreased anti-oxidant function and increased susceptibility to oxidative stress, thus making it a marker of cellular redox status. An imbalance in GSH/GSSG ratio has been implicated in the onset and progression of human diseases, such as neurodegenerative diseases, cancers, pulmonary diseases and cardiovascular diseases (Ballatori et al., 2009; Kalinina et al., 2014).


How It Is Measured or Detected

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GSH and GSSG levels can be determined by high-performance liquid chromatography HPLC, capillary electrophoresis, or biochemically in microplates. Several different assays have been designed to measure glutathione in samples. Enzyme recycling is a widely accepted method to determine total glutathione, in which GSH reacts with DTNB (Ellman's reagent) in the presence of glutathione reductase. Glutathione reductase reduces GSSG to GSH, which then reacts with DTNB to produce a yellow colored 5-thio-2-nitrobenzoic acid (TNB), which absorbs light at a wavelength of 412 nm (Tipple and Rogers, 2012). Another method uses HPLC separation and fluorometric detection, where iodoactetic acid is added as a thiol akylating agent followed by dansyl chloride derivatization for fluorometric detection. Similarly, monochlorobimane can be added to culture medium in order to form a fluorescent GSH-monochlorobimane adduct that can be measured fluorometrically (Kamencic et al., 2000).


Evidence Supporting Taxonomic Applicability

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The concentrations of GSH and GSSG have been shown in tissues of human and laboratory animals, including rats, mice and cows (Chen et al., 2010; Giustarini et al., 2013).


Evidence for Perturbation by Stressor



References

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Ballatori, N., Krance, S.M., Notenboom, S., Shi, S., Tieu, K., and Hammond, C.L. (2009). Glutathione dysregulation and the etiology and progression of human diseases. Biol. Chem. 390, 191–214.

Chen, C.-A., Wang, T.-Y., Varadharaj, S., Reyes, L.A., Hemann, C., Talukder, M.A.H., Chen, Y.-R., Druhan, L.J., and Zweier, J.L. (2010). S-glutathionylation uncouples eNOS and regulates its cellular and vascular function. Nature 468, 1115–1118.

Giustarini, D., Dalle-Donne, I., Milzani, A., Fanti, P., and Rossi, R. (2013). Analysis of GSH and GSSG after derivatization with N-ethylmaleimide. Nat. Protoc. 8, 1660–1669.

Kalinina, E.V., Chernov, N.N., and Novichkova, M.D. (2014). Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes. Biochem. Biokhimii︠a︡ 79, 1562–1583.

Kamencic, H., Lyon, A., Paterson, P.G., and Juurlink, B.H. (2000). Monochlorobimane fluorometric method to measure tissue glutathione. Anal. Biochem. 286, 35–37.

Tipple, T.E., and Rogers, L.K. (2012). Methods for the Determination of Plasma or Tissue Glutathione Levels. Methods Mol. Biol. Clifton NJ 889, 315–324.