Acceleration of phosphatidylcholine synthesis and breakdown by inhibitors of mitochondrial function in neuronal cells: a model of the membrane defect of Alzheimer's disease.
Brain cells in Alzheimer's disease (AD) exhibit a membrane defect characterized by accelerated phospholipid turnover. The mechanism responsible for this defect remains unknown. Recent studies indicate that impairment of mitochondrial function is frequently observed in AD and may be responsible for certain aspects of its pathophysiology. We show that when PC12 cells are exposed to inhibitors of mitochondrial bioenergetics, the turnover of their major membrane phospholipid, phosphatidylcholine, is accelerated, producing a pattern of metabolic changes that mimics that observed in brains of AD patients. Abnormalities of mitochondrial function may therefore underlie the membrane defect in AD.
Farber
S A
SA
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Slack
B E
BE
Blusztajn
J K
JK
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005997:Glycerylphosphorylcholine; D008566:Membranes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D010713:Phosphatidylcholines / Q000378:metabolism*; D010767:Phosphorylcholine / Q000378:metabolism; D051381:Rats; D019810:Sodium Azide / Q000494:pharmacology; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology*
D004140:Dinitrophenols; D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines; D014475:Uncoupling Agents; D010767:Phosphorylcholine; D003566:Cytidine Diphosphate Choline; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D005997:Glycerylphosphorylcholine; D019810:Sodium Azide; D002794:Choline