Magnone Maria Chiara, Langmesser Sonja, Bezdek April Candice, Tallone Tiziano, Rusconi Sandro, Albrecht Urs
Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland.
Front Neurol. 2015 Jan 13;5:289. doi: 10.3389/fneur.2014.00289. eCollection 2014.
Living in the earth's oxygenated environment forced organisms to develop strategies to cope with the damaging effects of molecular oxygen known as reactive oxygen species (ROS). Here, we show that Per2, a molecular component of the mammalian circadian clock, is involved in regulating a cell's response to oxidative stress. Mouse embryonic fibroblasts (MEFs) containing a mutation in the Per2 gene are more resistant to cytotoxic effects mediated by ROS than wild-type cells, which is paralleled by an altered regulation of bcl-2 expression in Per2 mutant MEFs. The elevated survival rate and alteration of NADH/NAD(+) ratio in the mutant cells is reversed by introduction of the wild-type Per2 gene. Interestingly, clock synchronized cells display a time dependent sensitivity to paraquat, a ROS inducing agent. Our observations indicate that the circadian clock is involved in regulating the fate of a cell to survive or to die in response to oxidative stress, which could have implications for cancer development and the aging process.
生活在地球的富氧环境中，迫使生物体形成应对分子氧破坏作用的策略，这种破坏作用被称为活性氧（ROS）。在此，我们表明，哺乳动物生物钟的分子成分Per2参与调节细胞对氧化应激的反应。与野生型细胞相比，含有Per2基因突变的小鼠胚胎成纤维细胞（MEF）对ROS介导的细胞毒性作用更具抗性，这与Per2突变型MEF中bcl-2表达的调节改变并行。通过引入野生型Per2基因，突变细胞中提高的存活率和NADH/NAD(+)比值的改变得以逆转。有趣的是，生物钟同步的细胞对百草枯（一种ROS诱导剂）表现出时间依赖性敏感性。我们的观察结果表明，生物钟参与调节细胞在氧化应激下的生死命运，这可能对癌症发展和衰老过程产生影响。
