title: Oxidized low density lipoprotein increases acetylcholinesterase activity correlating with reactive oxygen species production.
abstract: Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and oxidative stress are suspected to be a key combination in the onset of AD and acetylcholinesterase (AChE) plays a part in this pathology. The present study aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma cells in culture. Both mildly and fully oxidized human LDL (mox- and fox-LDL), but not native (non-oxidized) LDL were cytotoxic in dose- and time-dependent patterns and this was accompanied by an increased production of intracellular reactive oxygen species (ROS). Oxidized LDL (10-200 μg/mL) augmented AChE activity after 4 and 24h treatments, respectively while the native LDL was without effect. The increased AChE with oxidized LDLs was accompanied by a proportionate increase in intracellular ROS formation (R=0.904). These findings support the notion that oxidized LDLs are cytotoxic and that their action on AChE may reduce central cholinergic transmission in AD and affirm AChE as a continued rational for anticholinesterase therapy but in conjunction with antioxidant/antihyperlipidemic cotreatments.
authors.affiliation: Department of Pharmacy Practice and Center of Excellence for Innovation in Chemistry, Pharmacological Research Unit, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
authors.forename: Panit
authors.initials: P
authors.lastname: Yamchuen
authors.affiliation: Department of Pharmacy Practice and Center of Excellence for Innovation in Chemistry, Pharmacological Research Unit, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
authors.forename: Sathid
authors.initials: S
authors.lastname: Aimjongjun
authors.affiliation: Department of Pharmacy Practice and Center of Excellence for Innovation in Chemistry, Pharmacological Research Unit, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand. Electronic address: nanteetipl@nu.ac.th.
authors.forename: Nanteetip
authors.initials: N
authors.lastname: Limpeanchob
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Alzheimer’s disease; Hypercholesterolemia; Neuroblastoma cells; Oxidized low density lipoprotein; Reactive oxygen species