動物的冬眠堪稱生命過程中的奇跡。在極端惡劣的環(huán)境下,，一些冬眠動物靠維持接近零度的體溫以及近乎于正常情況下百分之一的心跳、呼吸和代謝來度過整個(gè)冬季,。更為有趣的是,，動物在冬眠中會進(jìn)行周期性自發(fā)覺醒。目前,，我們僅知道動物在冬眠過程中進(jìn)行了代謝重組并且啟動了組織保護(hù)等機(jī)制,，但對其分子機(jī)制的理解非常有限。
近日,，中科院上海生命科學(xué)研究院計(jì)算生物學(xué)所嚴(yán)軍課題組與生化與細(xì)胞所曾嶸組以及美國阿拉斯加大學(xué)Brian Barnes等人合作,，結(jié)合之前在動物冬眠中mRNA水平研究的基礎(chǔ)，系統(tǒng)研究了北極地鼠在冬眠中蛋白質(zhì)表達(dá)發(fā)生的整體變化,。在這項(xiàng)研究中,，該研究組通過計(jì)算手段構(gòu)建了全新的地鼠蛋白庫，并首次使用無標(biāo)記的高通量蛋白質(zhì)譜技術(shù)系統(tǒng)分析了北極地鼠在冬眠各個(gè)過程中蛋白質(zhì)水平的變化,。該工作共發(fā)現(xiàn)3000多個(gè)地鼠蛋白質(zhì),，其中517個(gè)蛋白質(zhì)在冬眠各個(gè)狀態(tài)比較中有顯著的差異，包括大量參與葡萄糖分解,、脂肪酸合成分解以及參與機(jī)體保護(hù)的蛋白質(zhì),。該研究發(fā)現(xiàn)動物在冬眠中周期性自發(fā)覺醒時(shí)，參與蛋白翻譯和降解,、mRNA加工以及氧化磷酸化的蛋白的表達(dá)量顯著上升而在mRNA水平卻沒有發(fā)現(xiàn)顯著差異,，即可能存在顯著的轉(zhuǎn)錄后調(diào)控。該研究于11月20日在線發(fā)表于國際著名學(xué)術(shù)期刊《分子與細(xì)胞蛋白質(zhì)組學(xué)》（Molecular & Cellular Proteomics）,。
值得指出的是,，很多人類疾病諸如心力衰竭、中風(fēng)等也是在類似動物冬眠的低溫、缺氧的環(huán)境壓力下產(chǎn)生的,。研究動物冬眠的機(jī)制有利于開發(fā)新一類藥物治療相關(guān)疾病,。
該研究工作得到了科技部、上海市科委,、美國自然科學(xué)基金的資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
