很多人都知道,我們每個人體內(nèi)的生物鐘可以幫助調(diào)節(jié)機體的多種生物反應(yīng),,但據(jù)賓夕法尼亞大學(xué)醫(yī)學(xué)院的研究人員發(fā)現(xiàn),,這二者之間可以相互影響——許多常見的生物學(xué)過程,如胰島素代謝等,也能反過來調(diào)節(jié)人體內(nèi)的生物鐘,。
這篇研究報告發(fā)表在本周的Cell雜志上,或許能夠給醫(yī)生提供某些啟示:可以利用某些小分子抑制或刺激生物過程,,以此來影響生物鐘,。
研究人員利用全基因組篩選,發(fā)現(xiàn)在控制生理周期長短的幾百個基因中,,減少任何一個基因的表達都會使生理周期發(fā)生重大的改變,。這些生物鐘相關(guān)的基因也參與到多種生物過程中,而且在胰島素代謝,,葉酸代謝以及細胞周期中,,也有大量的生物鐘相關(guān)基因,這表明這些過程與生物鐘有密切的關(guān)系,。
由于生物學(xué)過程可能對生物鐘產(chǎn)生反饋調(diào)節(jié),,研究人員Hogenesch想到了某些觀點。比如,,細胞分裂過程需要大量的能量,,但當(dāng)能量需求不足條件下,細胞自身必然會暫緩該過程,,暫緩也許是當(dāng)機體生物鐘面對資源短缺時,,細胞進化的一種策略。”
Hogenesch強調(diào),,雖然這項實驗表明,,生物過程和個體細胞生物鐘之間有一個反饋系統(tǒng),但該試驗是在培養(yǎng)條件下進行的,,因此還需進一步實驗證實這種生物反饋系統(tǒng)在生物體中也同樣存在,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.