Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17β

• Published in: Journal of Neural Transmission Vol. 108; no. 4; pp. 475 - 488
• Main Authors: KÖLSCH, H, LUDWIG, M, LÜTJOHANN, D, RAO, M. L
• Format: Journal Article
• Language: English
• Published: Wien Springer 02-04-2001; New York, NY
• Subjects: 24-Hydroxycholesterol; Biological and medical sciences; Medical sciences; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Oxidative stress; Toxicity; Estrogen; 17β-Estradiol; Lipids; Neuroprotective agent; Neuroblastoma; E-Vitamins; In vitro; Ovarian hormone; Cholesterol; Cell line; Sex steroid hormone; Apoptosis
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s007020170068

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 mu M) in that 75% of the cells survived. Physiological concentrations of estradiol-17 beta (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-17 beta treatment in the prevention and therapy of neurodegenerative disease.