Cited by 586Redox biology and oxidative stressAntioxidant Activity and Oxidative StressCell death mechanisms and regulation

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Maturation-Dependent Vulnerability of Oligodendrocytes to Oxidative Stress-Induced Death Caused by Glutathione Depletion

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Back, Stephen A., Gan, Xiaodong, Li, Ya, Rosenberg, Paul A., Volpe, Joseph J.·1998·The Journal of Neuroscience

DOI 10.1523/jneurosci.18-16-06241.1998PMC PMC6793198

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Abstract

Death of oligodendrocyte (OL) precursors can be triggered in vitro by cystine deprivation, a form of oxidative stress that involves depletion of intracellular glutathione. We report here that OLs demonstrate maturation-dependent differences in survival when subjected to free radical-mediated injury induced by glutathione depletion. Using immunopanning to isolate rat preoligodendrocytes (preOLs), we generated highly enriched populations of preOLs and mature OLs under chemically defined conditions. Cystine deprivation caused a similar decrease in glutathione levels in OLs at both stages. However, preOLs were completely killed by cystine deprivation, whereas mature OLs remained viable. Although the glutathione-depleting agents buthionine sulfoximine and diethylmaleate were more potent in depleting glutathione in mature OLs, both agents were significantly more toxic to preOLs. Glutathione depletion markedly increased intracellular free radical generation in preOLs, but not in mature OLs, as indicated by oxidation of the redox-sensitive probe dihydrorhodamine 123. The antioxidants alpha-tocopherol, idebenone, and glutathione monoethylester prevented the oxidation of dihydrorhodamine in cystine-depleted preOLs and markedly protected against cell death. When the intracellular glutathione level was not manipulated, preOLs were also more vulnerable than mature OLs to exogenous free radical toxicity generated by a xanthine-xanthine oxidase system. Ultrastructural features of free radical-mediated injury in glutathione-depleted preOLs included nuclear condensation, margination of chromatin, and mitochondrial swelling. These observations indicate that preOLs are significantly more sensitive to the toxic effects of glutathione depletion and that oligodendroglial maturation is associated with decreased susceptibility to oxidative stress.

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Authors: Back, S. A., Gan, X., Li, Y., Rosenberg, P. A., & Volpe, J. J.
Affiliations: Boston Children's Hospital (US)
ORCID: Back, Stephen A.
Li, Ya
Rosenberg, Paul A.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1998-08-15
Volume: 18
Issue: 16
Pages: 6241-6253
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.18-16-06241.1998
PMC: PMC6793198
OpenAlex: W2146317119
Cited by: 586
References: 62
Citations by year: 2026: 8 · 2025: 15 · 2024: 16 · 2023: 15 · 2022: 21 · 2021: 13 · 2020: 20 · 2019: 15 · 2018: 18 · 2017: 28 · 2016: 19 · 2015: 18 · 2014: 21 · 2013: 22 · 2012: 23
FWCI: 4.08
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p20ns032570-03, 5k08ns001855-06)
National Institute of Neurological Disorders and Stroke (NS 01855, P20 NS32570)
National Institute of Child Health and Human Development
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: oligodendrocyte precursor cells, oligodendrocyte maturation, glutathione depletion, oxidative stress, cystine deprivation, free radical toxicity, cell death, buthionine sulfoximine, diethyl maleate, alpha-tocopherol, idebenone, glutathione monoethyl ester, xanthine/xanthine oxidase, mitochondrial swelling, nuclear condensation, neuroprotection
MeSH terms: Animals, Cell Count, Cell Division, Cells, Cultured, Cystine, Free Radicals, Glutathione, Growth Substances, Oligodendroglia, Stem Cells, Free Radical Scavengers, Cellular Senescence, Cell Death, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Buthionine Sulfoximine, Rats

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Maturation-Dependent Vulnerability of Oligodendrocytes to Oxidative Stress-Induced Death Caused by Glutathione Depletion

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