Morphine induces Beclin 1-and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus
Zhao LX1,2; Zhu YS[*]1,3; Wang DM4; Chen M1; Gao P1; Xiao WM5; Rao GH3; Wang XH1; Jin HJ1; Xu L6; Sui N*4; Chen Q*1,3; zhuys@nankai.edu.cn, suin@psych.ac.cn and chenq@ioz.ac.cn
2010
发表期刊AUTOPHAGY
ISSN1554-8627
卷号6期号:3页码:386-394
合作性质其它
摘要Chronic exposure to morphine can induce drug addiction and neural injury, but the exact mechanism is not fully understood. Here we show that morphine induces autophagy in neuroblastoma SH-SY5Y cells and in the rat hippocampus. Pharmacological approach shows that this effect appears to be mediated by PTX-sensitive G protein-coupled receptors signaling cascade. Morphine increases Beclin 1 expression and reduces the interaction between Beclin 1 and Bcl-2, thus releasing Beclin 1 for its pro-autophagic activity. Bcl-2 overexpression inhibits morphine-induced autophagy, whereas knockdown of Beclin 1 or knockout of ATG5 prevents morphine-induced autophagy. In addition, chronic treatment with morphine induces cell death, which is increased by autophagy inhibition through Beclin 1 RNAi. Our data are the first to reveal that Beclin 1 and ATG5 play key roles in morphine-induced autophagy, which may contribute to morphine-induced neuronal injury.
关键词Morphine Autophagy Cell Death Beclin 1 Atg5
资助者This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui. ; This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui. ; This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui. ; This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui.
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收录类别SCI
语种英语
资助者This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui. ; This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui. ; This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui. ; This work is supported by a key project from the Natural Science Foundation China (No.30630038) and 973 program project (2006CB910102) awarded to Q. Chen, grants from Tianjin Natural Science Foundation (09JCZDJC21200) to Y. Zhu and from National Basic Research Program (2009CB522002) and the NNSF (30770719) to N. Sui.
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/5941
专题科研部门_学习记忆的分子神经机制(徐林)
科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者zhuys@nankai.edu.cn, suin@psych.ac.cn and chenq@ioz.ac.cn
作者单位1.Laboratory of Apoptosis and cancer Biology; The state Key Laboratory of Biomembrane and Membrane Biotechnology; institute of Zoology; chinese Academy of sciences; P.R. china
2.Graduate University of the chinese Academy of sciences; P.R. china
3.college of Life sciences; Nankai University; P.R. china
4.Key Laboratory of Mental health; institute of Psychology; chinese Academy of sciences; P.R. china
5.college of Life sciences; Peking University; P.R. china
6.Key Laboratory of Animal Models and human Disease Mechanisms; Kunming institute of Zoology; chinese Academy of sciences; Kunming, P.R. china
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Zhao LX,Zhu YS[*],Wang DM,et al. Morphine induces Beclin 1-and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus[J]. AUTOPHAGY,2010,6(3):386-394.
APA Zhao LX.,Zhu YS[*].,Wang DM.,Chen M.,Gao P.,...&zhuys@nankai.edu.cn, suin@psych.ac.cn and chenq@ioz.ac.cn.(2010).Morphine induces Beclin 1-and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus.AUTOPHAGY,6(3),386-394.
MLA Zhao LX,et al."Morphine induces Beclin 1-and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus".AUTOPHAGY 6.3(2010):386-394.
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