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  • Title: Morphine induces Beclin 1- and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus.
    Author: Zhao L, Zhu Y, Wang D, Chen M, Gao P, Xiao W, Rao G, Wang X, Jin H, Xu L, Sui N, Chen Q.
    Journal: Autophagy; 2010 Apr; 6(3):386-94. PubMed ID: 20190558.
    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.
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