Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran.
Drug Alcohol Depend. 2021 Oct 1;227:108982. doi: 10.1016/j.drugalcdep.2021.108982. Epub 2021 Aug 27.
Drug dependence promotes accelerated aging and higher mortality compare with the general population. Telomere length is a biomarker of determination of cellular aging. Telomere attrition has been reported in heroin dependent patients. To investigate whether telomere length is affected by morphine or not, the expressions of hTERT and TERF2 in morphine treated human SH-SY5Y cells were determined and compared with untreated cells.
The SH-SY5Y cells were treated with 1 and 5 μM concentrations of morphine for different exposure times (1d, 2d, 3d, 7d and 60 days). The mRNA levels of hTERT and TERF2 were determined using quantitative real-time RCR. The relative telomere length was measured as the ratio of telomere/36B4.
The hTERT and TERF2 mRNA levels were down regulated in morphine treated cells as a function of exposure duration. These alterations were reversible if morphine was removed from the culture medium. No reduction in the relative expression of hTERT and TERF2 in the cells exposed to N-acetyl cysteine (NAC) plus morphine was observed. In the SH-SY5Y cells treated by 5 μM morphine for 60 consecutive days, the hTERT and TERF2 mRNA levels and relative telomere lengths remarkably decreased.
Reversible alteration of mRNA levels by removing morphine from culture medium, and effect of NAC in co-treatment of morphine plus NAC, emphasize the role of reactive oxygen species in down-regulation of the expression of hTERT and TERF2 by morphine. Telomere attrition in morphine treated cells is a consequence of down-regulation of the expression of hTERT and TERF2.
与普通人群相比，药物依赖会促进衰老加速和死亡率升高。端粒长度是细胞衰老测定的生物标志物。已有研究报道海洛因依赖患者端粒缩短。为了研究吗啡是否会影响端粒长度，我们检测了吗啡处理的人 SH-SY5Y 细胞中 hTERT 和 TERF2 的表达，并与未处理的细胞进行比较。
用 1 和 5μM 浓度的吗啡处理 SH-SY5Y 细胞不同的暴露时间（1d、2d、3d、7d 和 60d）。用实时定量 PCR 检测 hTERT 和 TERF2 的 mRNA 水平。相对端粒长度通过端粒/36B4 的比值来衡量。
随着暴露时间的延长，吗啡处理的细胞中 hTERT 和 TERF2 的 mRNA 水平下调。如果从培养基中去除吗啡，这些变化是可逆的。在暴露于 N-乙酰半胱氨酸（NAC）加吗啡的细胞中，hTERT 和 TERF2 的相对表达没有减少。在连续 60 天用 5μM 吗啡处理的 SH-SY5Y 细胞中，hTERT 和 TERF2 的 mRNA 水平和相对端粒长度显著降低。
从培养基中去除吗啡可使 mRNA 水平发生可逆改变，而 NAC 在吗啡加 NAC 共同处理中的作用，强调了活性氧在吗啡下调 hTERT 和 TERF2 表达中的作用。吗啡处理细胞中端粒缩短是 hTERT 和 TERF2 表达下调的结果。
