tailieunhanh - Báo cáo khoa học: The proapoptotic member of the Bcl-2 family Bcl-2 / E1B-19K-interacting protein 3 is a mediator of caspase-independent neuronal death in excitotoxicity

Caspase-independent neuronal death has been shown to occur in neuroexci-totoxicity. Here, we tested the hypothesis that the gene encoding Bcl-2⁄E1B-19K-interacting protein 3 (BNIP3) mediates caspase-independent neuronal death in excitotoxicity. | IFEBS Journal The proapoptotic member of the Bcl-2 family Bcl-2 E1B-19K-interacting protein 3 is a mediator of caspase-independent neuronal death in excitotoxicity Zhengfeng Zhang1 2 Ruoyang Shi1 Jiequn Weng1 Xingshun Xu3 Xin-Min Li1 Tian-ming Gao4 and Jiming Kong1 4 1 Department of Human Anatomy and CellScience University of Manitoba Winnipeg Manitoba Canada 2 Department of Orthopedics Xinqiao Hospital TheThrid Military MedicalUniversity Chongqing China 3 Institute of Neuroscience Soochow University Suzhou Jiangsu Province China 4 Department of Anatomy and Neurobiology Southern MedicalUniversity Guangzhou China Keywords apoptosis Bcl-2 E1B-19K-interacting protein 3 BNIP3 caspase-independent cell death excitotoxicity neuron Correspondence J. Kong or T. Gao Department of Human Anatomy and CellScience University of Manitoba 730 William Avenue Winnipeg Manitoba R3E 0W3 Canada Department of Anatomy and Neurobiology Southern MedicalUniversity Guangzhou 510515 China Fax 1 204 789 3920 Tel 1 204 977 5601 011 86 20 6164 8216 E-mail kongj@ tianminggao@ Caspase-independent neuronal death has been shown to occur in neuroexci-totoxicity. Here we tested the hypothesis that the gene encoding Bcl-2 E1B-19K-interacting protein 3 BNIP3 mediates caspase-independent neuronal death in excitotoxicity. BNIP3 was not detectable in neurons under normal condition. BNIP3 expression was increased dramatically in neurons in both in vivo and in vitro models of excitotoxicity. Expression of full-length BNIP3 in primary hippocampal neurons induced atypical cell death that required protein synthesis but was largely independent of caspase activities. Inhibition of BNIP3 expression by RNA interference protected against glutamate-induced neuronal cell death. Thus BNIP3 activation and expression appears to be both necessary and sufficient for neuronal apoptosis in excitotoxicity. These results suggest that BNIP3 may be a new target for neuronal rescue strategies. Received 3 June