7alpha-Hydroperoxycholesterol causes CNS neuronal cell death.
Brain cholesterol, which is synthesized in the central nervous system and also partly taken up from lipoproteins via the blood-brain barrier, is a major component of neuronal membranes. Oxidation of cholesterol leads to the formation of oxysterols, which have been shown to act cytotoxic. The influence of 7alpha-hydroperoxycholesterol, was investigated using the human neuroblastoma cell line SH-SY5Y. 7alpha-Hydroperoxycholesterol caused neuronal cell death; this neurotoxic effect was dose-dependent, within 48 h 10 microM led to 50%, 50 microM to 92% loss of cell viability, which was detected by cell morphology and Trypan blue exclusion. DNA-fragmentation or caspase-3 activity were not detectable, LDH release occurred rapidly and reactive oxygen species (ROS) were generated. Therefore we infer that 7alpha-hydroperoxycholesterol, apart from its role in atherosclerosis, leads to necrosis of neuronal cells.
Kölsch
H
H
Department of Clinical Biochemistry, University of Bonn, Germany.
Ludwig
M
M
Lütjohann
D
D
Prange
W
W
Rao
M L
ML
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000633:toxicity; D006801:Humans; D009336:Necrosis; D009447:Neuroblastoma; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017382:Reactive Oxygen Species; C041011:cholesterol 7-hydroperoxide; D002784:Cholesterol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases