中科院极端环境蛋白表达波动研究取得进展

　　

生物通报道，据中科院消息，计算生物学所严军课题组与生化与细胞所曾嵘组以及美国阿拉斯加大学Brian Barnes等人在动物冬眠期间蛋白表达波动方面的研究取得了新的进展，相关成果文章Shotgun proteomic analysis of hibernating arctic ground squirrels发表在《Molecular & Cellular Proteomics》上。

 

该研究工作得到了科技部、上海市科委、美国自然科学基金的资助。

 

动物的冬眠堪称生命过程中的奇迹。在极端恶劣的环境下，一些冬眠动物靠维持接近零度的体温以及近乎于正常情况下百分之一的心跳、呼吸和代谢来度过整个冬季。更为有趣的是，动物在冬眠中会进行周期性自发觉醒。目前，我们仅知道动物在冬眠过程中进行了代谢重组并且启动了组织保护等机制，但对其分子机制的理解非常有限。

 

严军课题组与生化与细胞所曾嵘组等人，结合之前在动物冬眠中mRNA水平研究的基础，系统研究了北极地鼠在冬眠中蛋白质表达发生的整体变化。

 

在这项研究中, 该研究组通过计算手段构建了全新的地鼠蛋白库, 并首次使用无标记的高通量蛋白质谱技术系统分析了北极地鼠在冬眠各个过程中蛋白质水平的变化。该工作共发现3000多个地鼠蛋白质，其中517个蛋白质在冬眠各个状态比较中有显著的差异，包括大量参与葡萄糖分解、脂肪酸合成分解以及参与机体保护的蛋白质。

 

该研究发现动物在冬眠中周期性自发觉醒时, 参与蛋白翻译和降解、mRNA加工以及氧化磷酸化的蛋白的表达量显著上升而在mRNA水平却没有发现显著差异，即可能存在显著的转录后调控。

 

值得指出的是，很多人类疾病诸如心力衰竭、中风等也是在类似动物冬眠的低温、缺氧的环境压力下产生的。研究动物冬眠的机制有利于开发新一类药物治疗相关疾病。

 

严军   研究员

 

研究方向:

功能基因组学

 

研究领域:

我们主要采取高通量的测量、分析方法对一系列复杂的生理学过程的分子生物学原理进行系统研究。当前，我们研究的生理学过程主要包括哺乳动物中的冬眠、生物节律以及睡眠。我们对北极地鼠(Arctic ground squirrel)在冬眠过程中基因表达、蛋白表达、小RNA表达的变化进行了系统研究，发现一系列涉及新陈代谢、抗氧化物合成、输运、解毒、心肌收缩、肌肉退化、细胞凋亡、生物钟等重要功能的基因、蛋白、小RNA的表达在冬眠过程中发生显著的变化。 这些研究不但在很大程度上推进了对冬眠分子机制的理解，并且有助于设计新的药物以治疗人类在类似情况下引发的疾病。 在此基础上， 我们正在开展北美黑熊(American Black Bear)冬眠的研究。 我们对大量哺乳动物涉及生物节律的基因芯片数据进行了收集、整理和分析，对不同组织和物种中节律基因的节律峰点进行了比较。通过计算方法和实验数据的整合，系统地研究了转录因子调控在生物节律中所起的作用，以及环境因素对生物节律的影响。

 

发表论文(摘要):

[1] Guang-jiong Ni, Hong Guan, Wei-min Zhou, and Jun Yan, Antiparticle in the light of Einstein-Podolsky-Rosen Paradox and Klein Paradox, Chinese Physics Letters, Vol. 17, No. 6, 2000, 393-395

[2] Jun Yan, Harmonic Interaction Model and Its Applications in Bose-Einstein Condensation, Journal of Statistical Physics, Vol. 113, Nos. 3/4, Nov. 2003, 623-634

[3] K. K. Mon, J. K. Percus, and Jun Yan, Quasi One-Dimensional Self-Diffusion, Molecular Simulation, Vol. 29 (12), Dec. 2003, 721-726

[4] Jun Yan and Thomas G. Marr, Computational analysis of 3��-ends of ESTs shows four classes of alternative polyadenylation in human, mouse, and rat, Genome Research, Vol. 15, 2005, 369-375

[5] Jun Yan, Adlai Burman, Calen Nichols, Linda Alila, Louise C. Showe, Michael K. Showe, Bert B. Boyer, Brian M. Barnes, and Thomas G. Marr, Detection of differential gene expression in ?brown adipose tissue of hibernating arctic ground squirrels with mouse ?microarrays. Physiol Genomics 25: 346-353, 2006

 

生物通推荐原文检索

Shotgun proteomic analysis of hibernating arctic ground squirrels

Chunxuan Shao, Yuting Liu, Hongqiang Ruan, Ying Li, Haifang Wang, Franziska Kohl, Anna V. Goropashnaya, Vadim B. Fedorov, Rong Zeng, Brian M. Barnes, and Jun Yan

CAS-MPG Partner Institute for Computational Biology, Shanghai 200031

 

Corresponding Author: [e-mail]

 

Mammalian hibernation involves complex mechanisms of metabolic reprogramming and tissue protection. Previous gene expression studies of hibernation have mainly focused on changes at the mRNA level. Large-scale proteomic studies on hibernation have lagged behind, largely due to the lack of an adequate protein database specific for hibernating species. We constructed a ground squirrel protein database for protein identification and used a label-free shotgun proteomic approach to analyze protein expression throughout the torpor-arousal cycle during hibernation in arctic ground squirrels (Urocitellus parryii). We identified more than 3,000 unique proteins from livers of arctic ground squirrels. Among them, 517 proteins showed significant differential expression comparing animals sampled after at least 8 days of continuous torpor (late torpid), within 5 hours of a spontaneous arousal episode (early aroused), and 1-2 months after hibernation had ended (non-hibernating). Consistent with changes at the mRNA level shown in a previous study on the same tissue samples, proteins involved in glycolysis and fatty acid synthesis were significantly under-expressed at the protein level in both late torpid and early aroused animals compared to non-hibernating animals, whereas proteins involved in fatty acid catabolism were significantly over-expressed. On the other hand, when we compared late torpid and early aroused animals, there were discrepancies between mRNA and protein levels for a large number of genes. Proteins involved in protein translation and degradation, mRNA processing, and oxidative phosphorylation were significantly over-expressed in early aroused animals compared to late torpid animals, whereas no significant changes at the mRNA levels between these stages had been observed. Our results suggest that there is substantial post-transcriptional regulation of proteins during torpor-arousal cycles of hibernation.