Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17beta |
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Authors: | Kölsch H Ludwig M Lütjohann D Rao M L |
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Institution: | (1) Department of Clinical Biochemistry,,;(2) Department of Psychiatry and Psychotherapy, and,;(3) Department of Clinical Pharmacology, University of Bonn, Bonn, Federal Republic of Germany, DE |
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Abstract: | Summary. 24-Hydroxycholesterol, the main cholesterol elimination product of the brain is increased in serum of Alzheimer patients.
This oxysterol behaves neurotoxic towards the human neuroblastoma cell line, SH-SY5Y. Here we demonstrate, that 24-hydroxycholesterol-induced
neurotoxicity in differentiated SH-SY5Y cells was due to apoptosis, as indicated by DNA-fragmentation, caspase-3 activation
and a decrease of the mitochondrial membrane potential. Free radicals were generated, resulting in the death of 75% of the
cells within 48 h; neurotoxicity in differentiated SH-SY5Y cells was partially prevented by physiological concentrations of
vitamin E (50–100 μM) in that 75% of the cells survived. Physiological concentrations of estradiol-17β (1–100 nM) elicited
a protective effect in differentiated cells, which was not significant; however, in undifferentiated cells a significant protection
was noted by this steroid hormone. Vitamin C and melatonin did not prevent 24-hydroxycholesterol-induced neurotoxicity. These
in vitro data support the in vivo observed beneficial effects reported as circumstantial evidence of vitamin E and estradiol-17β
treatment in the prevention and therapy of neurodegenerative disease.
Received June 19, 2000; accepted November 20, 2000 |
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Keywords: | : 24-Hydroxycholesterol vitamin E estradiol-17β vitamin C melatonin apoptosis oxidative stress neuronal cells neuroprotection caspase-3 DNA-fragmentation mitochondrial membrane potential |
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