Cholesterol potentiates beta-amyloid-induced toxicity in human neuroblastoma cells: involvement of oxidative stress.
Alterations in brain cholesterol concentration and metabolism seem to be involved in Alzheimer's disease (AD). In fact, several experimental studies have reported that modification of cholesterol content can influence the expression of the amyloid precursor protein (APP) and amyloid beta peptide (Abeta) production. However, it remains to be determined if changes in neuronal cholesterol content may influence the toxicity of Abeta peptides and the mechanism involved. Aged mice, AD patients and neurons exposed to Abeta, show a significant increase in membrane-associated oxidative stress. Since Abeta is able to promote oxidative stress directly by catalytically producing H(2)O(2) from cholesterol, the present work analyzed the effect of high cholesterol incorporated into human neuroblastoma cells in Abeta-mediated neurotoxicity and the role of reactive oxygen species (ROS) generation. Neuronal viability was studied also in the presence of 24S-hydroxycholesterol, the main cholesterol metabolite in brain, as well as the potential protective role of the lipophilic statin, lovastatin.
Ferrera
Patricia
P
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, Mexico, DF, Mexico.
Mercado-Gómez
Octavio
O
Silva-Aguilar
Martín
M
Valverde
Mahara
M
Arias
Clorinda
C
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism*; D005372:Filipin / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008148:Lovastatin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D017382:Reactive Oxygen Species; D005372:Filipin; D002784:Cholesterol; D008148:Lovastatin