3H-1,2-dithiole-3-thione protects PC12 cells against amyloid beta 1-42 (Aβ1-42) induced apoptosis via activation of the ERK1/2 pathway

作者：Zhang, Chunyan; Xie, Linsen; Guan, Fangxia^*; Cui, Yuanbo^*

来源：Life Sciences, 2018, 213: 74-81.

DOI：10.1016/j.lfs.2018.10.025

• PC12 cells
• A beta
• Apoptosis
• D3T
• ERK1/2

Aims: Increasing evidence displays that deposition of aggregated beta-amyloid (A beta) leads to neuronal cell apoptosis, thus aggravates the pathological progression of Alzheimer's disease (AD). 3H-1,2-dithiole-3-thione (D3T) has been proved to exert neuroprotective effects. However, the effect of D3T on protecting against A beta-induced apoptosis and the underlying mechanism are unknown. @@@ Main methods: MTT, DCFH-DA assay, LDH release assay, Fluo-3 AM assay, Flow cytometry and Western blot were used to examine cell viability, ROS level, LDH release, intracellular Ca2+ concentration, cell apoptosis and related proteins level respectively. @@@ Key findings: In the present study, we found that D3T pretreatment significantly increased cell viability and decreased reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH) levels and the intracellular calcium concentration of rat pheochromocytoma (PC12) cells after A beta(1-42) exposure. In addition, D3T pretreatment inhibited A beta(1-42) induced cell apoptosis as well as protein levels of Bax and Caspase-3 in PC12 cells. Further, D3T markedly activated extracellular regulated protein kinase 1/2 (p-ERK1/2) but not PI3K/Akt signaling. Moreover, the protective effect of D3T against A beta(1-42) induced apoptosis was abolished by the ERK1/2 pathway inhibitor PD9805(while PI3K inhibitor LY294002 had no significant effect. @@@ Significance: Taken together, these findings suggest that D3T protects PC12 cells against A beta(1-42) induced apoptosis through activation of the ERK1/2 pathway.

• 出版日期2018-11-15
• 单位郑州大学