很多人都知道,我们每个人体内的生物钟可以帮助调节机体的多种生物反应,但据宾夕法尼亚大学医学院的研究人员发现,这二者之间可以相互影响——许多常见的生物学过程,如胰岛素代谢等,也能反过来调节人体内的生物钟。
这篇研究报告发表在本周的Cell杂志上,或许能够给医生提供某些启示:可以利用某些小分子抑制或刺激生物过程,以此来影响生物钟。
研究人员利用全基因组筛选,发现在控制生理周期长短的几百个基因中,减少任何一个基因的表达都会使生理周期发生重大的改变。这些生物钟相关的基因也参与到多种生物过程中,而且在胰岛素代谢,叶酸代谢以及细胞周期中,也有大量的生物钟相关基因,这表明这些过程与生物钟有密切的关系。
由于生物学过程可能对生物钟产生反馈调节,研究人员Hogenesch想到了某些观点。比如,细胞分裂过程需要大量的能量,但当能量需求不足条件下,细胞自身必然会暂缓该过程,暂缓也许是当机体生物钟面对资源短缺时,细胞进化的一种策略。”
Hogenesch强调,虽然这项实验表明,生物过程和个体细胞生物钟之间有一个反馈系统,但该试验是在培养条件下进行的,因此还需进一步实验证实这种生物反馈系统在生物体中也同样存在。(生物谷Bioon.com)
生物谷推荐原始出处:
Cell, 18 September 2009 doi:10.1016/j.cell.2009.08.031
A Genome-wide RNAi Screen for Modifiers of the Circadian Clock in Human Cells
Eric E. Zhang1, 2, 5, Andrew C. Liu1, 3, 5, Tsuyoshi Hirota1, 2, 5, Loren J. Miraglia1, Genevieve Welch1, Pagkapol Y. Pongsawakul2, Xianzhong Liu1, Ann Atwood2, Jon W. Huss1, Jeff Janes1, Andrew I. Su1, John B. Hogenesch4, , and Steve A. Kay2, ,
1 Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA
2 Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0130, USA
3 Department of Biology, The University of Memphis, Memphis, TN 38152, USA
4 Department of Pharmacology, Institute for Translational Medicine and Therapeutics, Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160, USA
Two decades of research identified more than a dozen clock genes and defined a biochemical feedback mechanism of circadian oscillator function. To identify additional clock genes and modifiers, we conducted a genome-wide small interfering RNA screen in a human cellular clock model. Knockdown of nearly 1000 genes reduced rhythm amplitude. Potent effects on period length or increased amplitude were less frequent; we found hundreds of these and confirmed them in secondary screens. Characterization of a subset of these genes demonstrated a dosage-dependent effect on oscillator function. Protein interaction network analysis showed that dozens of gene products directly or indirectly associate with known clock components. Pathway analysis revealed these genes are overrepresented for components of insulin and hedgehog signaling, the cell cycle, and the folate metabolism. Coupled with data showing many of these pathways are clock regulated, we conclude the clock is interconnected with many aspects of cellular function.