Induction of cytoprotective autophagy in PC-12 cells by cadmium
详细信息 查看全文
- 作者：Qiwen Wang ; Jiaqiao Zhu ; Kangbao Zhang ; Chenyang Jiang ; Yi Wang ; Yan Yuan ; Jianchun Bian ; Xuezhong Liu ; Jianhong Gu ; Zongping Liu
- 关键词：Cadmium ; Autophagy ; Apoptosis ; PC-12 cells ; LC3
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2013
- 出版时间：16 August, 2013
- 年：2013
- 卷：438
- 期：1
- 页码：186-192
- 全文大小：2542 K
文摘
Laboratory data have demonstrated that cadmium (Cd) may induce neuronal apoptosis. However, little is known about the role of autophagy in neurons. In this study, cell viability decreased in a dose- and time-dependent manner after treatment with Cd in PC-12 cells. As cells were exposed to Cd, the levels of LC3-II proteins became elevated, specific punctate distribution of endogenous LC3-II increased, and numerous autophagosomes appeared, which suggest that Cd induced a high level of autophagy. In the late stages of autophagy, an increase in the apoptosis ratio was observed. Likewise, pre-treatment with chloroquine (an autophagic inhibitor) and rapamycin (an autophagic inducer) resulted in an increased and decreased percentage of apoptosis in contrast to other Cd-treated groups, respectively. The results indicate that autophagy delayed apoptosis in Cd-treated PC-12 cells. Furthermore, co-treatment of cells with chloroquine reduced autophagy and cell activity. However, rapamycin had an opposite effect on autophagy and cell activity. Moreover, class III PI3 K/beclin-1/Bcl-2 signaling pathways served a function in Cd-induced autophagy. The findings suggest that Cd can induce cytoprotective autophagy by activating class III PI3 K/beclin-1/Bcl-2 signaling pathways. In sum, this study strongly suggests that autophagy may serve a positive function in the reduction of Cd-induced cytotoxicity.