title: Phosphatidylcholine protects neurons from toxic effects of amyloid β-protein in culture.
abstract: Amyloid β-protein (Aβ) is the major component of extracellular plaques in the brains of patients with Alzheimer's disease. It has been suggested that the interaction of Aβ with membrane cholesterol is essential for Aβ to exert neurotoxicity; however, the effect of phospholipids, another major membrane lipid component, on Aβ-induced neurotoxicity remains unclarified. Here we report the protective effect of phosphatidylcholine (PC) on primary cultured neurons against Aβ1-42-induced damage. Aβ1-42 caused neuronal death as demonstrated by lactose dehydrogenase (LDH) release, which was completely prevented by a pretreatment with PC in a dose-dependent manner. PC containing unsaturated long-chain acyl groups, 1,2-dioleoyl-PC (DOPC), also prevented neuronal death caused by Aβ1-42. The oleic acid ethyl-ester (OAEE) partially prevented Aβ1-42-induced neurotoxicity. Neurons that were pretreated with DOPC or OAEE for 24h, washed out, and exposed to Aβ1-42 in the absence of either of these reagents, were still resistant to Aβ1-42-induced neurotoxicity. In contrast, treatment with phosphotidylserine (PS) or docosahexaenoic acid etyl-ester (DHAEE) had no protective effect on neurons against Aβ1-42-induced damage. These results suggest that the control of cellular PC content, not PS content, may prove useful in the prevention or treatment of Alzheimer's disease.
authors.affiliation: Jeju Biodiversity Research Institute, JejuTechnopark, Jeju 699-943, Republic of Korea.
authors.forename: Mihee
authors.initials: M
authors.lastname: Ko
authors.affiliation: Laboratory of Molecular Biotechnology, Division of Molecular Cell Mechanisms, Department of Biological Mechanisms and Functions, Graduate School of Bio- and Agro-Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Biochemistry, Nagoya City University, Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdullah
authors.affiliation: Department of Biochemistry, Nagoya City University, Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Gong
authors.affiliation: Laboratory of Molecular Biotechnology, Division of Molecular Cell Mechanisms, Department of Biological Mechanisms and Functions, Graduate School of Bio- and Agro-Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Department of Biochemistry, Nagoya City University, Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: michi@med.nagoya-cu.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Michikawa
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D045022:Lactate Dehydrogenases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C075222:amyloid beta-protein (1-42); D045022:Lactate Dehydrogenases
keywords: Alzheimer's disease; Amyloid β-protein; Cholesterol; Neurotoxicity; Phosphatidylcholine; Phosphatidylserine