title: Butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one protects against amyloid-β peptides-induced cytotoxicity in PC12 cells.
abstract: Excessive extracellular deposition of amyloid-β peptides (Aβ) is a characteristic pathologic feature of Alzheimer's disease (AD). Accumulating evidence indicates that macroautophagy is involved in the pathogenesis of AD, but the exact role of macroautophapy is still unclear. We investigated whether Aβ(25-35) could cause reactive oxygen species (ROS) accumulation, decrease the activity of Na(+), K(+)-ATPase, trigger an autophagy process, and inhibit the growth of PC12 cells and examined the effect of a new autophagy modulator, butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3 H)-one (3BDO). 3BDO could block the decrease in cell viability induced by Aβ(25-35) by inhibiting ROS accumulation and the decrease in activity of Na(+), K(+)-ATPase and the autophagy process. In addition, 3BDO modulated the autophagy progress via a mammalian target of rampamycin-dependent pathway. 3BDO has a protective effect against the cytotoxicity induced by Aβ(25-35) and might be a promising tool for AD research.
authors: Department of Neural Medicine, Second Hospital of Shandong University, Jinan, China.
authors: ShaoNan
authors: S
authors: Yang
authors: ShengQing
authors: S
authors: Wang
authors: Nan
authors: N
authors: Peng
authors: ZhaoHong
authors: Z
authors: Xie
authors: Ping
authors: P
authors: Wang
authors: CuiPing
authors: C
authors: Zhao
authors: LiFei
authors: L
authors: Wei
authors: Hui
authors: H
authors: Yang
authors: BaoXiang
authors: B
authors: Zhao
authors: JunYing
authors: J
authors: Miao
authors: Jianzhong
authors: J
authors: Bi
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016716:PC12 Cells / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
chemical_list: D015107:4-Butyrolactone; D016229:Amyloid beta-Peptides; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D020123:Sirolimus; D000254:Sodium-Potassium-Exchanging ATPase; C553471:3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3H)-one; C526109:Anxa3 protein, rat; C074636:amyloid beta-protein (25-35)