Cobalt chloride induces PC12 cells apoptosis through reactive oxygen species and accompanied by AP-1 activation

✍ Scribed by Weiguo Zou; Mingda Yan; Weijing Xu; Hairong Huo; Lanying Sun; Zhongcheng Zheng; Xinyuan Liu

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 199 KB
• Volume: 64
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.1118

✦ Synopsis

Reactive oxygen species (ROS) are supposed to play an important role in hypoxia-and ischemia/reperfusionmediated neuronal injury with the characteristics of apoptosis. There are many reports showing that cobalt chloride (CoCl 2 ) could mimic the hypoxic responses in some aspects including production of ROS in cultured cells. The cytotoxicity of CoCl 2 and its molecular mechanisms have yet to be elucidated. We report that CoCl 2 triggered neuronal PC12 cells apoptosis in a dose-and time-dependent manner. Apoptosis was demonstrated by morphological changes and DNA fragmentation, and was dependent on macromolecular synthesis. Apoptosis was also confirmed by the decrease of the expression of Bcl-X L . To our knowledge, this is the first documentation of the apoptotic induction of CoCl 2 on PC12 cells. Furthermore, ROS production in PC12 cells was increased during CoCl 2 treatment. Antioxidants, which could inhibit ROS production, significantly blocked CoCl 2 -induced apoptosis, suggesting that apoptosis is mediated by ROS production. We also observed a significant increase of the DNA-binding activity of AP-1 in response to CoCl 2 and this increase was blocked by antioxidants, showing that CoCl 2 -induced apoptosis is accompanied by ROSactivated AP-1. CoCl 2 -treated PC12 cells may serve as an in vitro model for studies of molecular mechanisms in ROS-linked neuronal disorders.