@article{APS9339,
author = {Zheng MOU and Yu-he YUAN and Yu-xia LOU and Yang HENG and Ju-yang HUANG and Cong-yuan XIA and Yan GAO and Cheng-gen ZHU and Shi-feng CHU and Piao LUO and Jian-gong SHI and Nai-hong CHEN},
title = {Bibenzyl compound 20c protects against endoplasmic reticulum stress in tunicamycin-treated PC12 cells in vitro },
journal = {Acta Pharmacologica Sinica},
volume = {37},
number = {12},
year = {2017},
keywords = {},
abstract = {Aim: Accumulation of α-synuclein (α-syn) in the brain is a characteristic of Parkinson’s disease (PD). In this study, we investigated whether treatment with tunicamycin, an endoplasmic reticulum (ER) stress inducer, led to the accumulation of α-syn in PC12 cells, and where α-syn protein was accumulated, and finally, whether bibenzyl compound 20c, a novel compound isolated from Gastrodia elata (Tian ma), could alleviate the accumulation of α-syn and ER stress activation in tunicamycin-treated PC12 cells.
Methods: PC12 cells were treated with tunicamycin for different time (6 h, 12 h, 24 h, 48 h). Cell viability was determined by a MTT assay. Subcellular fractions of ER and mitochondria were extracted with the Tissue Endoplasmic reticulum Isolation Kit. The levels of α-syn protein and ER-stress-associated downstream chaperones were detected using Western blots and immunofluorescence.
Results: Treatment of PC12 cells with tunicamycin (0.5–10 μg/mL) dose-dependently increased the accumulation of α-syn monomer (19 kDa) and oligomer (55 kDa), and decreased the cell viability. Accumulation of the two forms of α-syn was observed in both the ER and mitochondria with increasing treatment time. Co-treatment with 20c (10-5 mol/L) significantly increased the viability of tunicamycintreated cells, reduced the level of α-syn protein and suppressed ER stress activation in the cells, evidenced by the reductions in phosphorylation of eIF2α and expression of spliced ATF6 and XBP1.
Conclusion: Tunicamycin treatment caused accumulation of α-syn monomer and oligomer in PC12 cells. Bibenzyl compound 20c reduces the accumulation of α-syn and inhibits the activation of ER stress, which protected PC12 cells against the toxicity induced by tunicamycin.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9339}
}