Cholesterol protects PC12 cells from beta-amyloid induced calcium disordering and cytotoxicity.
THE neurotoxic action of beta-amyloid seems to play an important role in the pathogenesis of Alzheimer's disease. The disruption of calcium homeostasis by beta-amyloid has been suspected to be the mechanism of its neurotoxicity. We found that beta-amyloid 25-35 induces a rapid increase in cytosolic calcium of PC12 cells, and subsequently, a dramatic decrease in cell viability. The increase in cytosolic calcium induced by beta-amyloid is effectively blocked by cholesterol in a dose-dependent manner. Furthermore, pretreatment of PC12 cells with cholesterol also significantly attenuates the neurotoxicity induced by beta-amyloid. These findings suggest that extracellular free cholesterol can protect neurones from beta-amyloid neurotoxicity mediated by the disruption of calcium homeostasis.
Zhou
Y
Y
Departments of Pharmacology, College of Medicine, University of Saskatchewan, Canada.
Richardson
J S
JS
D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects*; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D002784:Cholesterol; D002118:Calcium