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PNAS:揭示隐花色素可引发炎性疾病的分子机制

  1. PNAS
  2. 分子机制
  3. 引发
  4. 炎性疾病
  5. 隐花色素

来源:生物谷 2012-11-18 18:21

科学家们都知道切断机体的昼夜节律可以负向影响机体的化学作用,实际上,被夜班打乱作息周期的工人们更易于患慢性炎症疾病,比如糖尿病、肥胖甚至癌症。 近日,来自索尔克研究所的研究人员发现了一种联系昼夜节律紊乱和增加的炎症效应的分子,缺失了生物钟组分隐花色素(CRY)可以导致信号系统的激活,进而增加机体炎症分子的水平。相关研究成果刊登在了近日的国际杂志PNAS上。

科学家们都知道切断机体的昼夜节律可以负向影响机体的化学作用,实际上,被夜班打乱作息周期的工人们更易于患慢性炎症疾病,比如糖尿病、肥胖甚至癌症。

近日,来自索尔克研究所的研究人员发现了一种联系昼夜节律紊乱和增加的炎症效应的分子,缺失了生物钟组分隐花色素(CRY)可以导致信号系统的激活,进而增加机体炎症分子的水平。相关研究成果刊登在了近日的国际杂志PNAS上。

隐花色素(CRY)充当了节点的作用,来缓解生物钟活性,向生物机体传递信号;早晨,CRY就会停止抑制生物钟效应,帮助机体恢复效应来应对新的一天。为了深入研究生物钟组分在免疫功能中扮演的角色,研究者测定了缺失CRY基因的小鼠大脑下丘脑炎症介质的表达效应,通过一系列的实验,结果表明CRY缺失的小鼠机体中特定炎症蛋白的水平发生了明显的增加。

研究者Panda表示,我们的研究发现揭示了缺乏CRY可以激活某些促炎分子,揭示出了隐花色素在调节炎症细胞因子表达上的作用。同时研究者发现缺失隐花色素也可以激活NF-kB途径,前期研究揭示了抑制该途径或许是某些疾病的合适治疗方法,比如NF-kB可以在某些癌症如多发性骨髓瘤中被激活,这将影响骨髓中抵御感染的浆细胞,使其不断增殖。最后研究者表示,目前的目标是找出如何在短期内抑制NF-kB活性来治疗像糖尿病等疾病。(生物谷Bioon.com)

编译自:Molecular Link Between Circadian Clock Disturbances and Inflammatory Diseases Discovered

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.

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