title: Morphine induces Beclin 1- and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus.
abstract: 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.
authors.affiliation: 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.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhao
authors.forename: Yushan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Weiming
authors.initials: W
authors.lastname: Xiao
authors.forename: Guanhua
authors.initials: G
authors.lastname: Rao
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Haijing
authors.initials: H
authors.lastname: Jin
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Nan
authors.initials: N
authors.lastname: Sui
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D045744:Cell Line, Tumor / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; C545865:Atg5 protein, rat; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; D000071186:Beclin-1; C512829:Becn1 protein, rat; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009294:Narcotics; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D009020:Morphine