據(jù)美聯(lián)社報(bào)道,，《美國(guó)科學(xué)院學(xué)報(bào)》網(wǎng)絡(luò)版披露一項(xiàng)新發(fā)現(xiàn),，一種影響生物鐘蛋白質(zhì)可以調(diào)節(jié)睡眠，這有助于科學(xué)家找到與睡眠有關(guān)的疾病的更好的治療方案。
密歇根州和猶他州的研究人員表示發(fā)現(xiàn),，tau基因突變是CK1基因的一種突變，過(guò)去人們一直以為,，這種突變會(huì)降低基因的活性,，從而使體內(nèi)的生物鐘加快。但是,，這種基因突變并非減慢基因活性,，相反是增加了基因的活性，所以加快了人體內(nèi)的生物鐘,。如消沉和失眠等紊亂病癥的治療,，關(guān)鍵是要知道人體的生物鐘如何才能得到控制。
該研究由美國(guó)國(guó)立衛(wèi)生研究院,、漢茲門腫瘤研究所和斯隆基金會(huì)為這次研究資助完成,。
生物鐘-晝夜節(jié)律的基礎(chǔ)研究
·Cell：晝夜節(jié)律基因Clock實(shí)際上是乙?；D(zhuǎn)移酶
·蛋白質(zhì)降解和晝夜節(jié)律
·從多個(gè)振蕩器的協(xié)調(diào)到晝夜節(jié)律的產(chǎn)生
·哺乳動(dòng)物晝夜節(jié)律研究新發(fā)現(xiàn)
·生物鐘/晝夜節(jié)律的研究進(jìn)展
·專集：睡眠的神經(jīng)機(jī)制與功能
·視網(wǎng)膜上的一種蛋白質(zhì)可調(diào)節(jié)人體生物鐘
·Science：法國(guó)科學(xué)家發(fā)現(xiàn)生物鐘的調(diào)節(jié)新機(jī)制
·Cell：細(xì)胞周期的動(dòng)力學(xué)被揭示--阻尼震蕩模型
·可以調(diào)控的生物鐘
·哺乳動(dòng)物和果蠅有相同的生物鐘基因
·Cell：骨骼重塑受到生物鐘的影響
·《PNAS》：讀出你的生物鐘
·PKG對(duì)生物鐘的重要影響：晝夜交替的信號(hào)
·研究證實(shí)“永恒”基因在哺乳動(dòng)物生物鐘的關(guān)鍵作用
·持續(xù)黑暗下生物鐘如何維持?
·日科學(xué)家編制出老鼠生物鐘時(shí)刻表
·日學(xué)者以雞做實(shí)驗(yàn)發(fā)現(xiàn)熬夜使生物鐘紊亂原因
·SUMO化修飾與細(xì)胞的生物鐘
·生物鐘對(duì)植物基因表達(dá)的影響超過(guò)預(yù)想
·可以調(diào)控的生物鐘
·研究發(fā)現(xiàn)生物鐘對(duì)藍(lán)光最敏感
·生物鐘“鐘擺” 揭開(kāi)生物鐘神秘面紗
·我國(guó)科學(xué)家解生物鐘之謎：蛋白質(zhì)是動(dòng)力之源
·細(xì)胞層次上的生物節(jié)律
·我國(guó)科學(xué)家發(fā)現(xiàn)調(diào)節(jié)起搏細(xì)胞節(jié)律的新機(jī)制
·Current Biology：生理節(jié)律重置的雙重速度
·我國(guó)科學(xué)家解生物鐘之謎：蛋白質(zhì)是動(dòng)力之源
·日本科學(xué)家揭示生物鐘同步化的機(jī)制
·生物鐘與細(xì)胞分裂有聯(lián)系
生物鐘與疾病
·Science：生物鐘、鋰鹽和雙相障礙
·生物鐘基因控制著腫瘤生長(zhǎng),？
·抑癌基因攜帶生物鐘信息
·Nature：基因突變是引發(fā)家族睡眠狀態(tài)提前綜合征的原因
·急性心肌梗塞發(fā)病與季節(jié)氣候及晝夜變化的關(guān)系
·我國(guó)高原病流行病學(xué)規(guī)律基本摸清
·生物鐘研究促進(jìn)對(duì)人類疾病的深入了解
·生物鐘分子揭示出精神疾病根源
·哮喘病為何多在夜間發(fā)作,？
·人體生物鐘可能影響到藥物成癮
·美研究發(fā)現(xiàn)生物鐘可影響癌癥治療效果
·呼吸中樞與呼吸節(jié)律的形成
·美科學(xué)家說(shuō)心臟病多在上午發(fā)作緣于生物鐘
生物鐘相關(guān)圖片
生物鐘－圖片圖譜
The surprising discovery means scientists must change their approach to designing new drugs to treat jet lag, insomnia, some forms of depression, sleep problems in shift workers and other circadian rhythm disorders, according to researchers at the University of Utah's Huntsman Cancer Institute and the University of Michigan, Ann Arbor.
The study – which involved the so-called tau mutation that causes hamsters to have a 20-hour day instead of a 24-hour day – will be published online the week of July 3 in the journal Proceedings of the National Academy of Sciences.
The researchers discovered that what was previously believed about the tau mutation – that a decrease in gene activity sped up a mammal's internal clock – was incorrect. Instead, the mutation caused an increase in gene activity to speed up the clock, making the day two to four hours shorter for affected animals.
Previous work had indicated that the tau mutation occurred in a gene called casein kinase 1 epsilon (CK1) and that the mutation caused an 85 percent loss of gene activity. This, it was thought, explained why the hamster had a short day. But as it turns out, this idea was wrong.
"The key to developing treatments for problems like depression and insomnia – disorders influenced by circadian rhythm – is being able to predict how the body"s internal clock can be controlled,” says David Virshup, M.D., co-principal investigator on the project and a Huntsman Cancer Institute investigator. “If the working model is wrong, drugs will have the opposite effect.”
The new study involved the collaboration between University of Michigan mathematician Daniel Forger, Ph.D., assistant professor of mathematics, who had developed a computer simulation of the biological clock, and Virshup, who had previously done research on CK1’s effect on circadian rhythm and its role in cancer development. Disruption of circadian rhythms has been linked to cancer and diabetes as well as depression and sleep disorders.
Forger ran computer simulations of how the tau mutation influenced the mammalian body clock. The tau mutant hamster has a short day. When a simulation used the prevailing theory that the mutation decreased CK1 gene activity, the simulation predicted that the day for the hamster got longer. But when Forger ran a simulation based on the controversial idea that the tau mutation increased activity of the CK1 gene, the day did get shorter, just as it does in real hamsters with the tau mutation.
“So he concluded that the tau mutation must increase, not decrease, the activity of the CK1 gene,” contrary to the accepted wisdom, Virshup says.
Few people working in circadian rhythm were convinced that Forger’s mathematical model was correct. But the Huntsman Cancer Institute researchers were interested because their experiments also suggested the tau mutation increased rather than decreased activity of the CK1 gene.
Virshup, with members of his lab Monica Gallego, Ph.D.; Erik Eide, Ph.D.; and Margaret Woolf, had used a drug that inhibited CK1 on cultured rat cells. According to the published research, they expected the cells to have a shorter day, just like the mutant hamster. Instead, the cells had a longer day. They were ready to believe that Forger’s simulation could be proved.
A simple experiment showed them why the cells’ day got longer and why Forger’s simulation was correct.
The Virshup lab had already established a way to measure how quickly PER, one of the proteins responsible for running the biological clock, degraded. It is the disappearance of PER and a related protein from cells that resets the body’s internal clock to start a new day.
Forger’s simulation said the tau mutation would cause PER to go away more quickly. The old model said the mutation caused PER to build up more quickly. Virshup explains: “The mutation can’t do both. We put either the normal or the mutant CK1 gene into mouse cells, and then we watched what happened to PER stability.”
The results proved Forger’s prediction: the circadian rhythm within the mouse cells sped up because the mutant CK1 gene was more active, making the PER protein disappear more quickly. That would explain why a day for an animal with the tau mutation would last only 20 hours.
Virshup says his team has begun development of a mouse model so they can begin to test ways to regulate circadian rhythm based on their findings. That will be a necessary step before new drugs can be developed for disorders related to circadian rhythms.
Source: University of Utah
