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《Cancer Research on Prevention and Treatment》 2015-02
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Mechanism of TG2 Regulating Hypoxia-induced Apoptosis in Osteosarcoma Cell Line MG-63 by Mitochondrial Pathway

CAI Wentao;XIA Hong;CHEN Anming;Department of Orthopaedics,Hainan Provincial People's Hospital;Graduate School,Southern Medical University;Department of Orthopedics,General Hospital of Guangzhou Military Command of PLA;Department of Orthopaedic,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology;  
Objective To investigate the effect of transgiutaminase2(TG2) on hypoxia-induced apoptosis of osteosarcoma cell line MG-63 and the mechanism of TG2 inhibiting cell apoptosis by suppressing the release of Cytochrome C and regulating the expression and activity of Caspase-3. Methods The hypoxia culture model was established by a hypoxia incubator and divided into four groups, normoxia group, pure hypoxia group, control si RNA hypoxia group and TG2 si RNA hypoxia group. The expression of TG2, Cytochrome C and Caspase-3 as well as the apoptosis rate were observed at different hypoxia culture phases(6, 12, 24, 48, 72h). Microtiter plate assay was performed to monitor intracellular TG2 activity. Results Compared with normoxia group, the activity, m RNA level and protein expression of TG2 were increased remarkably with correspondence to the hypoxia time in the pure hypoxia group and control si RNA hypoxia group(P0.01). But Caspase-3 activity didn't change significantly. Similarly, the protein expression level of Caspase-3 and Cytochrome C in cytosol, as well as the apoptosis rate were increased slightly. In the TG2 si RNA hypoxia group, Caspase-3 activity, Cytochrome C protein expression and cell apoptosis rate were increased obviously(P0.01). Conclusion In the hypoxia condition, TG2 could inhibit the hypoxia-induced apoptosis through preventing Cytochrome C releasing into the cytosol and suppressing Caspase-3 activities.
【Fund】: 海南省医药卫生科研项目(14A210267);; 国家973计划课题(2002CB513107)
【CateGory Index】: R738.1
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