Hypothalamic proteome changes in response to nicotine and its withdrawal are potentially associated with alteration in body weight
Hypothalamic proteome changes in response to nicotine and its withdrawal are potentially associated with alteration in body weight
复制标题
尼古丁及其戒断反应引起的下丘脑蛋白质组变化可能与体重变化有关
DOI：
10.1016/j.jprot.2020.103633
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发表时间：
2020-03-01
影响因子：
3.3
通讯作者：
Long, Yue-Sheng
中科院分区：
文献类型：
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作者：
Gao, Mei-Mei;Hu, Fei;Long, Yue-Sheng
尼古丁是烟草中的主要成瘾成分，在吸烟和戒烟后的体重变化中起着重要作用。在这里，我们发现尼古丁治疗的小鼠体重减轻，尼古丁戒断导致体重增加。利用基于TMT的蛋白质组学分析，我们获得了不同的下丘脑蛋白质谱响应于尼古丁和其戒断。从下丘脑中共鉴定出5000种蛋白质，其中50种蛋白质在尼古丁治疗28天后发生改变，28种蛋白质在尼古丁戒断15天后发生改变。在改变的蛋白质中，CASP 3、LCMT 2、GRIN 2D、CCNT 2、FADS 3和MRPS 18 B在尼古丁和戒断反应中呈反向变化，与体重的变化一致。其中，CASP 3、LCMT 2、GRIN 2D和CCNT 2与多个GO术语和KEGG通路相关，这些通路与细胞凋亡、神经传递和代谢有关。进一步的蛋白质印迹和RT-qPCR分析证实，4种蛋白质CASP 3、LCMT 2、GRIN 2D和CCNT 2的水平，而不是它们的mRNA转录物，响应于尼古丁和戒断而改变。因此，本研究提供了尼古丁和戒断诱导的下丘脑蛋白质谱，并提示这些改变的蛋白质在体重变化中的潜在作用。意义：吸烟是危害人类健康的重要因素之一。大多数吸烟者的体重往往较低，戒烟往往导致超重或肥胖，这是吸烟者坚持吸烟的重要原因。众所周知，尼古丁是烟草中的关键成分，通过影响下丘脑功能而与体重变化相关。本研究通过TMT蛋白质组学分析，鉴定了尼古丁处理和戒断后下丘脑蛋白质表达的差异，发现4种尼古丁处理和戒断诱导的相反蛋白CASP 3、LCMT 2、GRIN 2D和CCNT 2参与了多个富集的GO和KEGG通路，这些通路与细胞凋亡、神经传递和代谢有关。我们的研究可能为进一步研究尼古丁和戒断诱导体重变化的分子机制提供新的靶点。
Nicotine, a major addictive component in tobacco, plays an important role in the changes of body weight upon smoking and its cessation. Here we showed that nicotine-treated mice exhibited weight loss and nicotine withdrawal led to weight gain. Using TMT-based proteomic analysis, we obtained the different hypothalamic protein profiles in response to nicotine and its withdrawal. A total of 5000 proteins were identified from the hypothalamus with 50 altered proteins upon 28 -day nicotine treatment and 28 altered proteins upon 15-day nicotine withdrawal. Of the altered proteins, CASP3, LCMT2, GRIN2D, CCNT2, FADS3 and MRPS18B were inversely changed in response to nicotine and withdrawal, coincidence with the change of body weight. Of them, CASP3, LCMT2, GRIN2D and CCNT2 were found to be associated with several GO terms and KEGG pathways linking with cell apoptosis, neurotransmission and metabolism. Further Western blot and RT-qPCR analyses confirmed that the levels of the 4 proteins CASP3, LCMT2, GRIN2D and CCNT2, instead of their mRNA transcripts, altered in response to nicotine and withdrawal. Thus this study provides nicotine- and withdrawal-induced hypothalamic protein profiles and suggests potential roles of these altered proteins in the change of body weight.Significance: Cigarette smoking is one of important factors harming human health. Most smokers tend to have lower body weights and smoking cessation often lead to overweight or obesity, which is an important reason for smokers to insist on smoking. It is known that nicotine, a critical component in tobacco, is associated with the alteration in body weight by affecting hypothalamic function. Through TMT-based proteomic analysis, this study identified differential hypothalamic protein profiles in response to nicotine treatment and its withdrawal, and 4 nicotine- and withdrawal-induced contrary proteins CASP3, LCMT2, GRIN2D and CCNT2 are involved in several enriched GO terms and KEGG pathways, which are associated with cell apoptosis, neurotransmission and metabolism. Our study may provide novel targets for further investigation of the molecular mechanisms of nicotine- and withdrawal-induced alteration in body weight.