title: Down-regulation of antioxidant genes in human SH-SY5Y cells after treatment with morphine.
abstract: OBJECTIVE
  Morphine strongly induces reactive oxygen species (ROS). The deleterious actions of morphine can be countered by antioxidant system. In the present study, we investigated the expression levels of nine antioxidant genes in human SH-SY5Y cells treated with morphine.
  
  
  METHODS
  The cells were treated with three final concentrations of morphine (1, 5, and 10 μmol) for four exposure times (1 h, 24 h, 72 h and 18 days). The mRNA levels were determined using quantitative real-time RCR.
  
  
  RESULTS
  Based on the alterations of mRNA levels, the genes might be categorized into three different groups: In the first group, the mRNA levels of the CAT, SOD1 and GSTM3 genes were significantly down-regulated in all examined experimental conditions. In the second group, the mRNA levels of SOD2, NQO1, GSTM2 and GSTO1 were initially increased and then decreased. In the third group, the mRNA levels of NQO2 and GSTP1, were initially increased and then reached to the control levels. The number of down-regulated genes were significantly increased as a function of exposure time (χ(2)=7.52, P=0.006). We investigated the effect of morphine (10 μmol) in the absence and presence of N-acetyl-cysteine (NAC, 1 mmol). The mRNA levels revealed significant differences between cells exposed to morphine and cells co-treated with morphine plus NAC. In cases that morphine increased the level of mRNAs, morphine plus NAC, result in decreased mRNA levels and vice versa.
  
  
  CONCLUSIONS
  These findings suggested that there are different pathways for regulation of antioxidant genes after SH-SY5Y cells exposed to morphine and morphine might act through inducing ROS.
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran.
authors.forename: Khyber
authors.initials: K
authors.lastname: Saify
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran.
authors.forename: Iraj
authors.initials: I
authors.lastname: Saadat
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran. Electronic address: saadat@shirazu.ac.ir.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Saadat
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009020:Morphine; D000111:Acetylcysteine
keywords: Antioxidant; Gene expression; Morphine; N-acetyl-cysteine; SH-SY5Y cell