Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes
Open accessAbstract
Oxidative mechanisms of injury are important in many neurological disorders, including hypoxic-ischemic brain damage. Cerebral palsy after preterm birth is hypothesized to be caused by hypoxic-ischemic injury of developing oligodendrocytes (OLs). Here we examined the developmental sensitivity of OLs to exogenous hydrogen peroxide (H2O2) with stage-specific rat oligodendrocyte cultures. We found that H2O2 itself or that generated by glucose oxidase was more toxic to developing than to mature OLs. Mature OLs were able to degrade H2O2 faster than developing OLs, suggesting that higher antioxidant enzyme activity might be the basis for their resistance. Catalase expression and activity were relatively constant during oligodendrocyte maturation, whereas glutathione peroxidase (GPx) was upregulated with a twofold to threefold increase in its expression and activity. Thus, it appeared that the developmental change in resistance to H2O2 was caused by modulation of GPx but not by catalase expression. To test the relative roles of catalase and GPx in the setting of oxidative stress, we measured enzyme activity in cells exposed to H2O2 and found that H2O2 induced a decrease in catalase activity in developing but not in mature OLs. Inhibition of GPx by mercaptosuccinate led to an increase in the vulnerability of mature OLs to H2O2 as well as a reduction in catalase activity. Finally, H2O2-dependent inactivation of catalase in developing OLs was prevented by the GPx mimic ebselen. These data provide evidence for a key role for GPx-catalase cooperativity in the resistance of mature OLs to H2O2-induced cell death.
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In vitro studies show that oligodendrocytes are susceptible to oxidative stress because of their high metabolic activity and iron content combined with low antioxidant levels.
“In vitro studies show that oligodendrocytes are susceptible to oxidative stress due to their high metabolic activity and iron content combined with low antioxidant levels (Back et al., 1998; Baud et al., 2004; Fragoso et al., 2004).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Baud et al., 2004
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- Authors
- Baud, O., Greene, A. E., Li, J., Wang, H., Volpe, J. J., & Rosenberg, P. A.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Rosenberg, Paul A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-02-18
- Volume
- 24
- Issue
- 7
- Pages
- 1531-1540
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6730475
- OpenAlex
- W2024367623
- Cited by
- 292
- References
- 46
- Citations by year
- 2026: 4 · 2025: 17 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 14 · 2020: 14 · 2019: 13 · 2018: 16 · 2017: 17 · 2016: 13 · 2015: 12 · 2014: 15 · 2013: 14 · 2012: 12
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS38475, P01NS038475)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD18655, P30HD018655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- glutathione peroxidase, catalase, hydrogen peroxide, oligodendrocyte maturation, oxidative stress, antioxidant enzymes, catalase inactivation, ebselen, mercaptosuccinic acid, hypoxic-ischemic brain injury, cerebral palsy, oxidative cell death, developmental vulnerability
- MeSH terms
- Animals, Catalase, Cell Differentiation, Cells, Cultured, Drug Resistance, Glutathione Peroxidase, Hydrogen Peroxide, Oligodendroglia, Peroxides, Time Factors, Up-Regulation, Oxidants, Rats, Sprague-Dawley, Apoptosis, Oxidative Stress, In Situ Nick-End Labeling, Rats
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