Involvement of mitochondrial- and Fas-mediated dual mechanism in CoCl2-induced apoptosis of rat PC12 cells.
Hypoxic/ischemic condition induces neuronal apoptotic events, which consequently lead to neuronal cell death. However, its specific mechanistic pathways remain obscure. Cobalt chloride (CoCl(2)) could mimic the hypoxic condition including the production of reactive oxygen species (ROS). In this report, we investigated the signal pathway of CoCl(2)-induced apoptosis in PC12 cells. The main mechanism for these apoptosis appeared to be mitochondria-mediated pathway accompanied with loss of the mitochondrial transmembrane potential (Delta Psi m) followed by cytochrome c release from the mitochondria into the cytosol, resulting in the activation of caspase-9 and caspase-3. Also, upregulation of pro-apoptotic protein Bax, and downregulation of anti-apoptotic protein Bcl-2 by presence of CoCl(2) appeared significantly and it might result in activating mitochondria-mediated apoptosis. We showed that expression of Fas and Fas ligand was upregulated and caspase-8 was significantly activated in CoCl(2)-induced apoptotic cells. In addition, ZB4, an antagonistic Fas-antibody, inhibited the activation of caspase-8 by CoCl(2), indicating that Fas receptor was involved in this pathway. These results demonstrate that CoCl(2) induce apoptosis in PC12 cells via different dual apoptosis pathway through death receptor as well as mitochondria.
Jung
Ji-Yeon
JY
College of Dentistry, Dental Science Research Institute, Chonnam National University, Gwang Ju 500-757, South Korea.
Kim
Won-Jae
WJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics; D003035:Cobalt / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D019014:fas Receptor
C491898:Fas protein, rat; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D003035:Cobalt; D020169:Caspases; C018021:cobaltous chloride