国产一级a片免费看高清,亚洲熟女中文字幕在线视频,黄三级高清在线播放,免费黄色视频在线看

打開(kāi)APP
userphoto
未登錄

開(kāi)通VIP,暢享免費(fèi)電子書(shū)等14項(xiàng)超值服

開(kāi)通VIP
mTOR 信號(hào)調(diào)節(jié)中樞和外周生物鐘


mTOR signaling regulates central and peripheral circadian clock function.


|核心內(nèi)容:

生物鐘協(xié)調(diào)生理和新陳代謝的各項(xiàng)平衡。mTOR (哺乳動(dòng)物/機(jī)械性雷帕霉素靶標(biāo))是一種主要的細(xì)胞內(nèi)傳感器,它整合了營(yíng)養(yǎng)和能量狀態(tài)來(lái)調(diào)節(jié)蛋白質(zhì)合成、代謝和細(xì)胞生長(zhǎng)。以前的研究已經(jīng)證實(shí) mTOR 在調(diào)節(jié)視交叉上核中樞生物鐘的感光卷吸和同步化過(guò)程中起著關(guān)鍵作用。鑒于 mTOR 活動(dòng)在包括 SCN 在內(nèi)的各種組織和細(xì)胞中表現(xiàn)出強(qiáng)大的晝夜節(jié)律振蕩,我們?cè)谶@里繼續(xù)研究 mTOR 在協(xié)調(diào)中樞和外周晝夜振蕩器的自主生物鐘功能中的作用。

抑制mTOR會(huì)延長(zhǎng)周期,降低振幅

結(jié)合遺傳學(xué)和藥理學(xué)的方法,我們發(fā)現(xiàn) mTOR 調(diào)節(jié)內(nèi)在的時(shí)鐘特性,包括周期和振幅。在肝細(xì)胞和脂肪細(xì)胞周?chē)镧娔P椭校琺TOR 抑制延長(zhǎng)周期和抑制振幅,而 mTOR 活化縮短周期和增加振幅。Tsc2-/-成纖維細(xì)胞中 mTOR 的組成性激活提高了包括 CRY1、 BMAL1和 CLOCK 在內(nèi)的核心鐘蛋白水平。血清刺激誘導(dǎo)成纖維細(xì)胞 CRY1上調(diào),呈 mTOR 依賴但 Bmal1-和周期無(wú)關(guān)的方式。與細(xì)胞生物鐘模型的結(jié)果一致,mTOR 擾動(dòng)也調(diào)節(jié)體外 SCN 和肝臟生物鐘的周期和振幅。此外,mTOR 雜合子小鼠在恒定的黑暗和恒定的光照條件下都表現(xiàn)出運(yùn)動(dòng)活動(dòng)的晝夜節(jié)律時(shí)間延長(zhǎng)。綜上所述,這些結(jié)果支持了 mTOR 在晝夜節(jié)律計(jì)時(shí)和連接代謝狀態(tài)和晝夜節(jié)律生物鐘功能方面的重要作用。
原文摘要:

The circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient and energy status to regulate protein synthesis, metabolism, and cell growth. Previous studies have identified a key role for mTOR in regulating photic entrainment and synchrony of the central circadian clock in the suprachiasmatic nucleus (SCN). Given that mTOR activities exhibit robust circadian oscillations in a variety of tissues and cells including the SCN, here we continued to investigate the role of mTOR in orchestrating autonomous clock functions in central and peripheral circadian oscillators. Using a combination of genetic and pharmacological approaches we show that mTOR regulates intrinsic clock properties including period and amplitude. In peripheral clock models of hepatocytes and adipocytes, mTOR inhibition lengthens period and dampens amplitude, whereas mTOR activation shortens period and augments amplitude. Constitutive activation of mTOR in Tsc2-/-fibroblasts elevates levels of core clock proteins, including CRY1, BMAL1 and CLOCK. Serum stimulation induces CRY1 upregulation in fibroblasts in an mTOR-dependent but Bmal1- and Period-independent manner. Consistent with results from cellular clock models, mTOR perturbation also regulates period and amplitude in the ex vivo SCN and liver clocks. Further, mTOR heterozygous mice show lengthened circadian period of locomotor activity in both constant darkness and constant light. Together, these results support a significant role for mTOR in circadian timekeeping and in linking metabolic states to circadian clock functions.

參考文獻(xiàn):https://dx.doi.org/10.1371/journal.pgen.1007369

-------------------------------------------------------------------------

本站僅提供存儲(chǔ)服務(wù),所有內(nèi)容均由用戶發(fā)布,如發(fā)現(xiàn)有害或侵權(quán)內(nèi)容,請(qǐng)點(diǎn)擊舉報(bào)。
打開(kāi)APP,閱讀全文并永久保存 查看更多類(lèi)似文章
猜你喜歡
類(lèi)似文章
生物鐘基因與非酒精性脂肪性肝病
Science特刊:失眠、肥胖、癌癥……萬(wàn)能的生物鐘如何掌管我們的身體?
晝夜節(jié)律與腸道健康
盤(pán)點(diǎn) | 自然的饋贈(zèng)—生物鐘背后隱藏的奧秘
Nature子刊:為了生存,癌細(xì)胞“悄然”改變生物鐘
【生物鐘與癌癥】生物鐘與腫瘤發(fā)生
更多類(lèi)似文章 >>
生活服務(wù)
分享 收藏 導(dǎo)長(zhǎng)圖 關(guān)注 下載文章
綁定賬號(hào)成功
后續(xù)可登錄賬號(hào)暢享VIP特權(quán)!
如果VIP功能使用有故障,
可點(diǎn)擊這里聯(lián)系客服!

聯(lián)系客服