Hu Kong-He, Li Wen-Xue, Sun Min-Ying, Zhang She-Bing, Fan Cai-Xia, Wu Qiang, Zhu Wei, Xu Xin
Cell Physiol Biochem. 2015;36(2):642-54. doi: 10.1159/000430127.
BACKGROUND/AIMS: Cadmium (Cd) induces apoptosis in different kinds of cells, including osteoblasts, both in vivo and in vitro. However, little is known about the mechanisms by which Cd induces apoptosis.
In the present study, we used the human osteosarcoma cell line MG63, which has characteristics similar to human osteoblasts, as an in vitro model to determine the cellular mechanisms by which Cd induces apoptosis.
We found that short-term exposure to CdCl2 induced apoptosis in MG63 cells. Furthermore, the incubation of cells with CdCl2 significantly increased the level of phosphorylated p38MAPK and significantly decreased the phosphorylation of ERK1/2 in a concentration-dependent manner. Additionally, the inhibition of the phosphorylation of p38 MAPK by SB202190 protected MG63 cells from Cd-induced apoptosis. The incubation of MG63 cells with the ERK1/2 inhibitor PD98059 significantly increased apoptosis in MG63 cells. CdCl2 also significantly increased the intracellular levels of ROS. N-acetylcysteine (NAC) significantly reduced ROS levels and reversed the effects of CdCl2 on MAPK signaling.
Our results suggested that Cd induced apoptosis in MG63 cells by increasing ROS, activation of p38 MAPK and inhibition of ERK1/2 pathways.
背景/目的：镉（Cd）在体内和体外均可诱导包括成骨细胞在内的多种细胞发生凋亡。然而，关于Cd诱导凋亡的机制知之甚少。
在本研究中，我们使用具有与人成骨细胞相似特征的人骨肉瘤细胞系MG63作为体外模型，以确定Cd诱导凋亡的细胞机制。
我们发现短期暴露于CdCl₂可诱导MG63细胞凋亡。此外，用CdCl₂孵育细胞可显著增加磷酸化p38MAPK的水平，并以浓度依赖的方式显著降低ERK1/2的磷酸化水平。此外，SB202190抑制p38 MAPK的磷酸化可保护MG63细胞免受Cd诱导的凋亡。用ERK1/2抑制剂PD98059孵育MG63细胞可显著增加MG63细胞的凋亡。CdCl₂还显著增加细胞内活性氧（ROS）水平。N-乙酰半胱氨酸（NAC）显著降低ROS水平，并逆转CdCl₂对MAPK信号通路的影响。
我们的结果表明，Cd通过增加ROS、激活p38 MAPK和抑制ERK1/2信号通路诱导MG63细胞凋亡。
