Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran.
Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran.
Life Sci. 2016 Jan 1;144:26-9. doi: 10.1016/j.lfs.2015.11.014. Epub 2015 Nov 17.
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.
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.
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.
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.
吗啡强烈诱导活性氧（ROS）。抗氧化系统可以对抗吗啡的有害作用。在本研究中，我们研究了用吗啡处理的人 SH-SY5Y 细胞中 9 种抗氧化基因的表达水平。
用三种最终浓度的吗啡（1、5 和 10 μmol）处理细胞 4 个暴露时间（1 h、24 h、72 h 和 18 天）。使用定量实时 RCR 测定 mRNA 水平。
基于 mRNA 水平的变化，这些基因可能分为三组：第一组 CAT、SOD1 和 GSTM3 基因的 mRNA 水平在所有检测到的实验条件下均显著下调。第二组 SOD2、NQO1、GSTM2 和 GSTO1 的 mRNA 水平先升高后降低。第三组 NQO2 和 GSTP1 的 mRNA 水平先升高，然后达到对照水平。随着暴露时间的延长（χ(2)=7.52，P=0.006），下调基因的数量显著增加。我们研究了吗啡（10 μmol）在无和有 N-乙酰半胱氨酸（NAC，1 mmol）存在下的作用。暴露于吗啡的细胞和用吗啡加 NAC 共同处理的细胞之间的 mRNA 水平显示出显著差异。在吗啡增加 mRNA 水平的情况下，吗啡加 NAC 导致 mRNA 水平降低，反之亦然。
这些发现表明，SH-SY5Y 细胞暴露于吗啡后，抗氧化基因的调控存在不同的途径，而吗啡可能通过诱导 ROS 起作用。
