Pathophysiology Department, School of Basic Medical College, Tianjin Medical University, Tianjin, China; Department of Physiology, Zunyi Medical University, Zunyi, China.
Pathophysiology Department, School of Basic Medical College, Tianjin Medical University, Tianjin, China.
Chem Biol Interact. 2019 Sep 1;310:108688. doi: 10.1016/j.cbi.2019.06.001. Epub 2019 Jun 4.
Glucagon-like peptide 1 (GLP-1) has neuroprotective properties in Alzheimer's disease (AD). In this study, our aim is to explore the neuroprotective effects of liraglutide, a GLP-1 analogue, on AD-like neurodegeneration induced by HO in human neuroblastoma SH-SY5Y cells. Cytotoxicity was determined by MTT assay and lactate dehydrogenase level was monitored by LDH assay. The level of lipid peroxidation and cell apoptosis rate were measured by malondialdehyde (MDA) assay and Annexin V-FITC/propidium iodide (PI) staining. Western blotting was used to assess the expression of Bcl-2, Bax, caspase-3, tau and the Akt/GSK-3β. Liraglutide pre-treatment enhanced cell viability with reduced cytotoxicity, lipid peroxidationand and apoptosis. In addition, pre-treatment of liraglutide displayed that increased the expression of the pro-survival Bcl-2 and reduced pro-apoptotic Bax with ameliorated the hyperphosphorylation of tau and Akt/GSK-3β signaling pathway in HO stressed SH-SY5Y cells. These finding provided evidences that liraglutide protected the HO induced AD-like neurodegeneration through improving Akt/GSK-3β signaling pathway. These results suggest that liraglutide may have potential values for the treatment for AD.
胰高血糖素样肽 1（GLP-1）在阿尔茨海默病（AD）中具有神经保护作用。在这项研究中，我们的目的是探索利拉鲁肽（一种 GLP-1 类似物）对人神经母细胞瘤 SH-SY5Y 细胞中 HO 诱导的 AD 样神经退行性变的神经保护作用。通过 MTT 测定法测定细胞毒性，通过 LDH 测定法监测乳酸脱氢酶水平。通过丙二醛（MDA）测定法和 Annexin V-FITC/碘化丙啶（PI）染色测定脂质过氧化和细胞凋亡率。通过 Western blot 测定法评估 Bcl-2、Bax、caspase-3、tau 和 Akt/GSK-3β的表达。利拉鲁肽预处理可增强细胞活力，降低细胞毒性、脂质过氧化和细胞凋亡。此外，利拉鲁肽预处理显示，HO 应激 SH-SY5Y 细胞中促生存的 Bcl-2 表达增加，促凋亡的 Bax 表达减少，tau 和 Akt/GSK-3β信号通路的过度磷酸化得到改善。这些发现为利拉鲁肽通过改善 Akt/GSK-3β信号通路保护 HO 诱导的 AD 样神经退行性变提供了证据。这些结果表明，利拉鲁肽可能对 AD 的治疗具有潜在价值。
