Protocatechuic acid attenuates β-secretase activity and okadaic acid-induced autophagy via the Akt/GSK-3β/MEF2D pathway in PC12 cells

被引:18
作者
Huang, Liping [1 ]
Zhong, Xiaoqin [2 ,3 ,4 ]
Qin, Shaochen [5 ]
Deng, Minzhen [2 ,3 ,4 ]
机构
[1] Lingnan Normal Univ, Sch Chem & Chem Engn, Zhanjiang 524048, Guangdong, Peoples R China
[2] Guangdong Prov Hosp Chinese Med, Dept Neurol, 111 Dade Rd, Guangzhou 510120, Guangdong, Peoples R China
[3] Guangdong Prov Acad Chinese Med Sci, Guangzhou 510006, Guangdong, Peoples R China
[4] Guangzhou Univ Chinese Med, Clin Coll 2, Guangzhou 510120, Guangdong, Peoples R China
[5] Shanxi Univ Chinese Med, Dept Neurol, Affiliated Hosp, Taiyuan 030024, Shanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
protocatechuic acid; Alzheimer's disease; autophagy; METHYLENE-BLUE; MEF2D; ASARONE; RATS; NEUROTOXICITY; INHIBITION; LEVEL;
D O I
10.3892/mmr.2019.10905
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Okadaic acid (OA) can be used to induce an Alzheimer's disease (AD) model characterized by tau hyperphosphorylation, the formation of neurofibrillary tangles formation and beta-amyloid (A beta) deposition. Previous studies have shown that the upregulation of Beclin-1-dependent autophagy may contribute to the elimination of aggregated A beta. However, the effects of protocatechuic acid (PA) on the levels of A beta(42), phosphorylated (p)-tau and beta-secretase in OA-induced cell injury are unclear, and little is known concerning the role of the PA signaling pathway in the regulation of autophagy. The present study aimed to determine whether PA protects cells from OA-induced cytotoxicity via the regulation of Beclin-1-dependent autophagy and its regulatory signaling pathway. PC12 cells were treated with OA with or without PA for 24 h. Enzymatic assays were performed to measure p-tau, A beta 42 and beta-secretase activity. Western blotting was performed to detect p-Akt, p-glycogen synthase kinase-3 beta (p-GSK-3 beta), Akt, GSK-3 beta, myocyte enhancer factor 2D (MEF2D) and Beclin-1 protein expression levels. Immunofluorescence and immunocytochemistry were used to measure Beclin-1 expression levels. The results from this study showed that PA could increase cell viability and significantly decrease the levels of A beta(42), p-tau, beta-secretase and Beclin-1. PA can also promote the expression of p-Akt and MEF2D while suppressing the expression of p-GSK-3 beta. These results indicated that PA protects PC12 cells from OA-induced cytotoxicity, and attenuates autophagy via regulation of the Akt/GSK-3 beta/MEF2D pathway, therefore potentially contributing to the neuroprotective effects of PA against OA toxicity. These findings suggested that PA may have potential as a drug candidate in preventative AD therapy.
引用
收藏
页码:1328 / 1335
页数:8
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