科學(xué)家們都知道切斷機(jī)體的晝夜節(jié)律可以負(fù)向影響機(jī)體的化學(xué)作用，實際上,，被夜班打亂作息周期的工人們更易于患慢性炎癥疾病，比如糖尿病、肥胖甚至癌癥。
近日,，來自索爾克研究所的研究人員發(fā)現(xiàn)了一種聯(lián)系晝夜節(jié)律紊亂和增加的炎癥效應(yīng)的分子，缺失了生物鐘組分隱花色素（CRY）可以導(dǎo)致信號系統(tǒng)的激活,，進(jìn)而增加機(jī)體炎癥分子的水平,。相關(guān)研究成果刊登在了近日的國際雜志PNAS上。
隱花色素（CRY）充當(dāng)了節(jié)點(diǎn)的作用,，來緩解生物鐘活性,，向生物機(jī)體傳遞信號；早晨,，CRY就會停止抑制生物鐘效應(yīng),，幫助機(jī)體恢復(fù)效應(yīng)來應(yīng)對新的一天。為了深入研究生物鐘組分在免疫功能中扮演的角色,，研究者測定了缺失CRY基因的小鼠大腦下丘腦炎癥介質(zhì)的表達(dá)效應(yīng),，通過一系列的實驗，結(jié)果表明CRY缺失的小鼠機(jī)體中特定炎癥蛋白的水平發(fā)生了明顯的增加,。
研究者Panda表示,，我們的研究發(fā)現(xiàn)揭示了缺乏CRY可以激活某些促炎分子，揭示出了隱花色素在調(diào)節(jié)炎癥細(xì)胞因子表達(dá)上的作用,。同時研究者發(fā)現(xiàn)缺失隱花色素也可以激活NF-kB途徑，前期研究揭示了抑制該途徑或許是某些疾病的合適治療方法,，比如NF-kB可以在某些癌癥如多發(fā)性骨髓瘤中被激活,，這將影響骨髓中抵御感染的漿細(xì)胞，使其不斷增殖,。最后研究者表示,，目前的目標(biāo)是找出如何在短期內(nèi)抑制NF-kB活性來治療像糖尿病等疾病。（生物谷Bioon.com）
編譯自：Molecular Link Between Circadian Clock Disturbances and Inflammatory Diseases Discovered
doi:10.1073/pnas.1209965109
PMC:
PMID:
Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines
Rajesh Narasimamurthya, Megumi Hatorib, Surendra K. Nayakb, Fei Liua, Satchidananda Pandab,1, and Inder M. Vermaa,1
Chronic sleep deprivation perturbs the circadian clock and increases susceptibility to diseases such as diabetes, obesity, and cancer. Increased inflammation is one of the common underlying mechanisms of these diseases, thus raising a hypothesis that circadian-oscillator components may regulate immune response. Here we show that absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. We observed a constitutive NF–κB and protein kinase A (PKA) signaling activation in Cry1−/−;Cry2−/− cells. We further demonstrate that increased phosphorylation of p65 at S276 residue in Cry1−/−;Cry2−/− cells is due to increased PKA signaling activity, likely induced by a significantly high basal level of cAMP, which we detected in these cells. In addition, we report that CRY1 binds to adenylyl cyclase and limits cAMP production. Based on these data, we propose that absence of CRY protein(s) might release its (their) inhibition on cAMP production, resulting in elevated cAMP and increased PKA activation, subsequently leading to NF–κB activation through phosphorylation of p65 at S276. These results offer a mechanistic framework for understanding the link between circadian rhythm disruption and increased susceptibility to chronic inflammatory diseases.
