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Oxidative stress induced by ascorbate causes neuronal damage in an in vitro system
1Department of Physiology, Botterell Hall, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
Brain Research
|March 22, 2001
Summary
Ascorbic acid (ascorbate) can cause oxidative stress and cell damage in the brain, particularly after stroke. This occurs when its oxidized form enters neurons via glucose transporters, leading to harmful redox reactions.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Ascorbate (ionized ascorbic acid) has reducing properties but can induce oxidative stress and apoptosis.
- Brain ascorbate is released during hypoxia (e.g., stroke) and oxidized in plasma.
- Oxidized ascorbate (dehydroascorbate) enters neurons via glucose transporters (GLUT) during reperfusion.
Purpose of the Study:
- To investigate the mechanism of ascorbate-induced oxidative stress in neurons.
- To determine the role of glucose transporters (GLUT) in dehydroascorbate uptake and subsequent cellular damage.
Main Methods:
- Utilized rat cortical slices to study oxidative stress markers.
- Employed wortmannin, a phosphatidylinositol (PI)-3-kinase inhibitor, to investigate GLUT translocation.
- Measured cellular glutathione (GSH) content, lipid peroxide production, and ceramide accumulation.
Main Results:
- Ascorbate treatment decreased GSH and increased lipid peroxides in cortical slices.
- Wortmannin inhibited ascorbate-induced GSH decrease and lipid peroxidation but not H(2)O(2)-induced stress.
- Oxidative stress correlated with ceramide accumulation, suggesting GLUT-mediated dehydroascorbate uptake causes neuronal damage.
Conclusions:
- Glucose transporters (GLUT) efficiently transport dehydroascorbate into neurons.
- This uptake triggers redox reactions leading to oxidative stress, cellular damage, and apoptosis.
- Findings highlight a potential mechanism for neuronal injury following stroke and reperfusion.