Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17beta.
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 48h; neurotoxicity in differentiated SH-SY5Y cells was partially prevented by physiological concentrations of vitamin E (50-100 microM) in that 75% of the cells survived. Physiological concentrations of estradiol-17beta (1-100nM) 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-17beta treatment in the prevention and therapy of neurodegenerative disease.
Kölsch
H
H
Department of Clinical Biochemistry, University of Bonn, Federal Republic of Germany.
Ludwig
M
M
Lütjohann
D
D
Rao
M L
ML
D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000633:toxicity*; D008550:Melatonin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D005609:Free Radicals; D006888:Hydroxycholesterols; D014810:Vitamin E; C044563:24-hydroxycholesterol; D004958:Estradiol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D008550:Melatonin; D001205:Ascorbic Acid