title: Methamphetamine-mediated modulation of MOR expression in the SH-SY5Y neuroblastoma cell line.
abstract: 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.
authors.affiliation: Institute of NeuroImmune Pharmacology and Department of Biological Sciences, Seton, Hall University, South Orange, New Jersey 07079, USA.
authors.forename: Erik F
authors.initials: EF
authors.lastname: Langsdorf
authors.forename: Sulie L
authors.initials: SL
authors.lastname: Chang
mesh_terms: D000704:Analysis of Variance; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology*; D018613:Microscopy, Confocal / Q000379:methods; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D020112:Rhodamine 123 / Q000378:metabolism; D013997:Time Factors; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D000697:Central Nervous System Stimulants; D017382:Reactive Oxygen Species; D017450:Receptors, Opioid, mu; D014801:Vitamin A; D020112:Rhodamine 123; D008694:Methamphetamine; D006861:Hydrogen Peroxide; D004298:Dopamine