Institute of Biological Science and Bioengineering, Beijing Jiaotong University, Beijing 100044, China.
Neurosci Lett. 2011 Feb 11;489(3):168-71. doi: 10.1016/j.neulet.2010.12.009. Epub 2010 Dec 13.
Our previous genetic and proteomic studies demonstrated that dynamin 1 is significantly associated with nicotine dependence (ND) in human smokers and its expression is highly modulated by nicotine in the brains of animals. To provide further molecular evidence for the involvement of dynamin 1 in the etiology of ND, we investigated the regulatory effect of nicotine on the expression of dynamin 1 using both in vivo and in vitro approaches. With quantitative real-time RT-PCR, we found that dynamin 1 mRNA was significantly downregulated, by 30%, 31%, and 38%, in the striatum, hippocampus, and medial basal hypothalamus (MBH), respectively, of nicotine-treated rats (P<0.01 for all three regions). Further, dynamin 1 protein was downregulated by nicotine in the ventral tegmental area (VTA: 39.5%; P<0.01), hippocampus (13.4%, P<0.05), MBH (24.6%, P<0.01), and amygdala (15.7%, P<0.05). We also determined the effect of nicotine on human SH-SY5Y cells and found that dynamin 1 mRNA was significantly down-regulated by nicotine after treatment (51.4%; P<0.01), and a consistent decrease in the amount of the protein was also observed (36.6%; P<0.05). Taken together, our findings provide further molecular evidence for the involvement of dynamin 1 in the etiology of ND.
我们之前的遗传和蛋白质组学研究表明，动力蛋白 1 与人类吸烟者的尼古丁依赖（ND）显著相关，其表达在动物大脑中受到尼古丁的高度调节。为了提供更多分子证据表明动力蛋白 1 参与 ND 的发病机制，我们使用体内和体外方法研究了尼古丁对动力蛋白 1 表达的调节作用。通过定量实时 RT-PCR，我们发现尼古丁处理的大鼠纹状体、海马体和内侧基底部下丘脑（MBH）中 dynamin 1 mRNA 分别显著下调 30%、31%和 38%（三个区域均 P<0.01）。此外，尼古丁下调 VTA（39.5%；P<0.01）、海马体（13.4%，P<0.05）、MBH（24.6%，P<0.01）和杏仁核（15.7%，P<0.05）中的 dynamin 1 蛋白。我们还确定了尼古丁对人 SH-SY5Y 细胞的影响，发现尼古丁处理后 dynamin 1 mRNA 显著下调（51.4%；P<0.01），并且观察到蛋白量也一致减少（36.6%；P<0.05）。综上所述，我们的研究结果为 dynamin 1 参与 ND 的发病机制提供了更多的分子证据。
