据美联社报道，《美国科学院学报》网络版披露一项新发现，一种影响生物钟蛋白质可以调节睡眠，这有助于科学家找到与睡眠有关的疾病的更好的治疗方案。
密歇根州和犹他州的研究人员表示发现，tau基因突变是CK1基因的一种突变，过去人们一直以为，这种突变会降低基因的活性，从而使体内的生物钟加快。但是，这种基因突变并非减慢基因活性，相反是增加了基因的活性，所以加快了人体内的生物钟。如消沉和失眠等紊乱病症的治疗，关键是要知道人体的生物钟如何才能得到控制。
该研究由美国国立卫生研究院、汉兹门肿瘤研究所和斯隆基金会为这次研究资助完成。
生物钟-昼夜节律的基础研究
·Cell：昼夜节律基因Clock实际上是乙酰化转移酶
·蛋白质降解和昼夜节律
·从多个振荡器的协调到昼夜节律的产生
·哺乳动物昼夜节律研究新发现
·生物钟/昼夜节律的研究进展
·专集：睡眠的神经机制与功能
·视网膜上的一种蛋白质可调节人体生物钟
·Science：法国科学家发现生物钟的调节新机制
·Cell：细胞周期的动力学被揭示--阻尼震荡模型
·可以调控的生物钟
·哺乳动物和果蝇有相同的生物钟基因
·Cell：骨骼重塑受到生物钟的影响
·《PNAS》：读出你的生物钟
·PKG对生物钟的重要影响：昼夜交替的信号
·研究证实“永恒”基因在哺乳动物生物钟的关键作用
·持续黑暗下生物钟如何维持?
·日科学家编制出老鼠生物钟时刻表
·日学者以鸡做实验发现熬夜使生物钟紊乱原因
·SUMO化修饰与细胞的生物钟
·生物钟对植物基因表达的影响超过预想
·可以调控的生物钟
·研究发现生物钟对蓝光最敏感
·生物钟“钟摆” 揭开生物钟神秘面纱
·我国科学家解生物钟之谜：蛋白质是动力之源
·细胞层次上的生物节律
·我国科学家发现调节起搏细胞节律的新机制
·Current Biology：生理节律重置的双重速度
·我国科学家解生物钟之谜：蛋白质是动力之源
·日本科学家揭示生物钟同步化的机制
·生物钟与细胞分裂有联系
生物钟与疾病
·Science：生物钟、锂盐和双相障碍
·生物钟基因控制着肿瘤生长？
·抑癌基因携带生物钟信息
·Nature：基因突变是引发家族睡眠状态提前综合征的原因
·急性心肌梗塞发病与季节气候及昼夜变化的关系
·我国高原病流行病学规律基本摸清
·生物钟研究促进对人类疾病的深入了解
·生物钟分子揭示出精神疾病根源
·哮喘病为何多在夜间发作？
·人体生物钟可能影响到药物成瘾
·美研究发现生物钟可影响癌症治疗效果
·呼吸中枢与呼吸节律的形成
·美科学家说心脏病多在上午发作缘于生物钟
生物钟相关图片
生物钟－图片图谱
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
