Oxidative stress in cultured cerebral endothelial cells induces chromosomal aberrations, micronuclei, and apoptosis
Abstract
There is evidence accumulating that brain microvasculature is involved critically in oxidative stress‐mediated brain damage. Cultured cerebral microvascular endothelial cells were used to demonstrate the cytotoxic and genotoxic effects elicited by hypoxia/reoxygenation and DMNQ treatment in vitro. In addition, the effect of glucose deprivation during oxidative insult was assessed. The parameters determined were: 1) chromosomal aberrations; 2) induction of micronuclei; and 3) apoptosis. Our results indicate that both the exposure of the cerebral endothelial cells to 24 hr of hypoxia followed by 4 hr of reoxygenation, and treatment with the redox cycling quinone DMNQ, increased markedly the occurrence of chromosomal aberrations and micronuclei. It was found that expression of p53 was induced by oxidative stress, particularly when glucose had been omitted from the culture medium. Aglycemic culture conditions in general exacerbated the cytotoxic effects of oxidative insults, as evidenced by the increase in apoptotic cells and the decrease in the mitotic index. Interestingly, neither an elevation of cell lysis nor an increase in necrosis has been observed during our experiments. In summary, our data indicate that oxidative stress exerts considerable genotoxic and cytotoxic effects on cerebral endothelial cells, which might contribute to the progression of tissue damage in the central nervous system. © 2003 Wiley‐Liss, Inc.
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Oxidative stress caused by hypoxia-reoxygenation in endothelial cells can induce chromosomal aberrations such as dicentric chromosomes and micronuclei.
“Oxidative stress by hypoxia-reoxygenation in endothelial cells may induce more profound damage, such as chromosomal aberrations (e.g., dicentric chromosomes) and micronuclei [26].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [26]
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DNA damage responses to oxidative stress
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- Authors
- Bresgen, N., Karlhuber, G., Krizbai, I., Bauer, H., Bauer, H. C., & Eckl, P. M.
- Affiliations
- University of Salzburg (AT)
- Institute of Biophysics (HU)
- Corresponding author
- Eckl, P.M.
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2003-03-07
- Volume
- 72
- Issue
- 3
- Pages
- 327-333
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2014521862
- Cited by
- 58
- References
- 32
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 1
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- oxidative stress, brain microvascular endothelial cells, hypoxia/reoxygenation, chromosomal abnormalities, micronuclei, apoptosis, p53 expression, glucose deprivation, genotoxicity, cytotoxicity, cerebral microvasculature, brain damage
- MeSH terms
- Animals, Hypoxia, Cells, Cultured, Chromosome Aberrations, Endothelium, Vascular, Glucose, L-Lactate Dehydrogenase, Naphthoquinones, Swine, Telencephalon, Time Factors, Blotting, Western, Reperfusion Injury, Tumor Suppressor Protein p53, Apoptosis, Oxidative Stress, Micronuclei, Chromosome-Defective, Rats
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