Lithium differentially affects clock gene expression in serum-shocked NIH-3T3 cells
Lithium differentially affects clock gene expression in serum-shocked NIH-3T3 cells
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DOI：
10.1177/0269881110379508
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发表时间：
2011-07-01
影响因子：
4.1
通讯作者：
Steen, Vidar M.
中科院分区：
文献类型：
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作者：
Osland, Teresa M.;Ferno, Johan;Steen, Vidar M.
双相情感障碍与昼夜节律紊乱有关。锂经常用于双相情感障碍的长期治疗，并已被证明可以延长动物和人类的这种节律。为了研究锂是否会影响生物钟调控基因的表达，我们通过血清电击同步培养的NIH-3T3细胞，并检测生物钟基因Period1 （Per1）、Period2 （Per2）、Period3 （Per3）、Cryptochrome1 （Cry1）、Cryptochrome2 （Cry2）、脑和肌肉的烃核易位样1 （Bmal1）、昼夜运动输出周期kaput （clock）、rev - erbb - α (Nr1d1)、rar相关孤儿受体α (Ror-alpha)、糖原合成酶激酶3 β (Gsk-3 β)、酪蛋白激酶1-epsilon （CK1-epsilon; Csnk1 epsilon）、E4结合蛋白4 （E4BP4; nfil3）和白蛋白d结合蛋白（Dbp）在锂（20mM）或载体（20mM NaCl）存在下连续三天检测。我们发现，锂显著提高了Per2和Cry1的表达，而降低了Per3、Cry2、Bmal1、E4BP4和rev - erbb -alpha的表达。我们还发现锂延长了Per2的周期。综上所述，这些对生物钟基因表达的影响可能与锂对生物节律的影响有关，也可能为进一步探索其在治疗双相情感障碍中的情绪稳定作用提供新的线索。
Bipolar disorder has been associated with disturbances in circadian rhythms. Lithium is frequently used in the long-term treatment of bipolar disorder, and has been shown to prolong such rhythms in animals and humans. To examine whether lithium affects the expression of genes regulating the circadian clock, cultured NIH-3T3 cells were synchronized by serum-shocking, and the relative expression of the clock genes Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Brain and muscle aryl hydrocarbon nuclear translocator-like 1 (Bmal1), Circadian locomotor output cycles kaput (Clock), Rev-Erb-alpha (Nr1d1), RAR-related orphan receptor alpha (Ror-alpha), Glycogen synthase kinase-3 beta (Gsk-3 beta), Casein kinase 1-epsilon (CK1-epsilon; Csnk1 epsilon), E4 binding protein 4 (E4BP4; Nfil-3) and albumin D-binding protein (Dbp) was examined for three consecutive days in the presence of lithium (20 mM) or vehicle (20mM NaCl). We found that lithium significantly increased the expression of Per2 and Cry1, whereas Per3, Cry2, Bmal1, E4BP4 and Rev-Erb-alpha expression was reduced. We also found that lithium prolonged the period of Per2. Taken together, these effects on clock gene expression may be relevant for the effects of lithium on biological rhythms and could also give new leads to further explore its mood-stabilizing actions in the treatment of bipolar disorder.