title: Increased expression of Beclin-1-dependent autophagy protects against beta-amyloid-induced cell injury in PC12 cells [corrected].
abstract: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease. Beta-amyloid (Aβ) plays an important role in the pathogenesis of AD. Autophagy is a self-degradative process and its related protein Beclin-1 is involved in the initiation of autophagy. However, the role of Beclin-1 in the pathogenesis of AD is rarely reported. In this study, we examined cell viability and medium levels of neuron-specific enolase (NSE) in PC12 cells incubated with gradient concentrations of Aβ(1-42) (0.625, 1.25, 2.5, 5, 10 μM) for 6, 12, 24, 48, and 72 h, drew the index changes curves, and investigated the correlation between them. The result showed that cell viability was negatively correlated with NSE levels. Based on this study, Beclin-1 expression was quantitatively detected in Aβ1-42-treated PC12 cells and the dynamic changes curve of Beclin-1 was drawn from 3 to 72 h. Beclin-1 expression was positively correlated with cell viability. Furthermore, both autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin were used to investigate the effect of autophagy on Aβ(1-42)-induced cell injury. Aβ(1-42)-induced Beclin-1 expression was further upregulated by rapamycin but was downregulated by 3-MA. Moreover, cell viability was increased by rapamycin but was decreased by 3-MA, and NSE was decreased by rapamycin but was increased by 3-MA, suggesting that activation of Beclin-1-dependent autophagy before the damage occurred can prevent neuronal cell death, while inhibition of Beclin-1-dependent autophagy can hastened cell death. These findings indicate that increasing Beclin-1-dependent autophagy may have a preventive effect before the AD occurred.
authors: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 16, Jichang Road, Guangzhou, 510405, China.
authors: Zhongfeng
authors: Z
authors: Xue
authors: Sheng
authors: S
authors: Zhang
authors: Liping
authors: L
authors: Huang
authors: Yuping
authors: Y
authors: He
authors: Ruoming
authors: R
authors: Fang
authors: Yongqi
authors: Y
authors: Fang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D016923:Cell Death; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C025946:3-methyladenine; D010751:Phosphopyruvate Hydratase; D000225:Adenine; D020123:Sirolimus