Institute of NeuroImmune Pharmacology and Department of Biological Sciences, Seton, Hall University, South Orange, New Jersey 07079, USA.
Synapse. 2011 Sep;65(9):858-65. doi: 10.1002/syn.20913. Epub 2011 Mar 28.
Methamphetamine (METH) has been shown to induce oxidative stress in SH-SY5Y cells, a neuroblastic, dopaminergic cell line model. In neuronal cells, oxidation of dopamine by auto-oxidative or enzymatic mechanisms leads to the production of reactive oxygen species (ROS). Neuronal cells treated with METH accumulate dopamine, which can ultimately lead to increased levels of ROS. ROS has been shown to mediate the expression of the mu-opioid receptor (MOR). The goal of this in vitro study was to examine the effects of METH on the accumulation of intracellular ROS in SH-SY5Y cells, which could, in turn, modulate MOR expression. Confocal laser scanning microscopy (CLSM) indicated that METH induced intracellular accumulation of ROS, detected as increased fluorescence of rhodamine 123, in a dose- and time-dependent manner. Moreover, accumulation of ROS preceded METH-induced expression of the MOR, which was attenuated by the free radical chelator, vitamin E. Additionally, increased MOR expression was noted following hydrogen peroxide treatment, indicating a role for ROS in mediating MOR expression. Taken together, our data show that METH's effect on MOR expression is dependent upon sublethal levels of intracellular ROS, which suggests a possible coupling of METH- and opiate-mediated intracellular signaling.
甲基苯丙胺（METH）已被证明可诱导 SH-SY5Y 细胞（一种神经母细胞、多巴胺能细胞系模型）发生氧化应激。在神经元细胞中，多巴胺通过自动氧化或酶促机制氧化会导致活性氧（ROS）的产生。用 METH 处理的神经元细胞会积累多巴胺，这最终可能导致 ROS 水平升高。ROS 已被证明可介导μ-阿片受体（MOR）的表达。本体外研究的目的是研究 METH 对 SH-SY5Y 细胞内 ROS 积累的影响，这反过来又可以调节 MOR 的表达。共聚焦激光扫描显微镜（CLSM）表明，METH 以剂量和时间依赖的方式诱导细胞内 ROS 的积累，表现为罗丹明 123 荧光强度增加。此外，ROS 的积累先于 METH 诱导的 MOR 表达，而自由基清除剂维生素 E 可减弱这种诱导。此外，过氧化氢处理后观察到 MOR 表达增加，表明 ROS 在介导 MOR 表达中起作用。总之，我们的数据表明，METH 对 MOR 表达的影响取决于细胞内 ROS 的亚致死水平，这表明 METH 和阿片类药物介导的细胞内信号之间可能存在偶联。
