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。
近日，中科院上海生命科学研究院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等人合作，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。该研究于11月20日在线发表于国际著名学术期刊《分子与细胞蛋白质组学》（Molecular & Cellular Proteomics）。
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。
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。（生物谷Bioon.com）
生物谷推荐原始出处：
Mol. Cell. Proteomics, Nov 2009; doi:10.1074/mcp.M900260-MCP200
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
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.
