Circadian expression of clock genes in human oral mucosa and skin : Association with specific cell-cycle phases
Circadian expression of clock genes in human oral mucosa and skin : Association with specific cell-cycle phases
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DOI：
10.1016/s0002-9440(10)64135-1
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发表时间：
2001-05-01
影响因子：
6
通讯作者：
Ben-David, Y
中科院分区：
文献类型：
--
作者：
Bjarnason, GA;Jordan, RCK;Ben-David, Y
我们研究了从8名健康的每日活跃的男性研究参与者的口腔粘膜和皮肤中获得的活检组织中在一个24小时内时钟基因的相对RNA表达。我们发现人类时钟基因hClock、hTim、hPer1、hCry 1和hBmal 1在口腔粘膜和皮肤中表达，其昼夜节律特征与啮齿动物视交叉上核和外周组织中发现的昼夜节律特征一致。hPer1、hCry1和hBmal1具有节律性表达，分别在清晨、下午晚些时候和晚上达到峰值，而hClock和hTim不是节律性的。这是第一个显示啮齿动物中记录的所有五个时钟基因表达的昼夜节律谱的人类研究，表明它们在人类中的功能重要性。hPer1是一种DNA合成的标志物，具有昼夜节律变化，其活性高峰出现在下午早些时候，这与我们先前对人类口腔粘膜细胞周期定时的研究中的S期时间相一致。在口腔粘膜中，hPer1表达的主峰与G（1）期的峰值出现在一天中的同一时间，这表明生物钟与哺乳动物细胞周期之间可能存在联系。
We studied the relative RNA expression of clock genes throughout one 24-hour period in biopsies obtained from the oral mucosa and skin from eight healthy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that found in the suprachiasmatic nuclei and the peripheral tissues of rodents. hPer1, hCry1, and hBmal1 have a rhythmic expression peaking early in the morning, in late afternoon, and at night, respectively, whereas hClock and hTim are not rhythmic, This is the first human study to show a circadian profile of expression for all five clock genes as documented in rodents, suggesting their functional importance Fn man. In concurrent oral mucosa biopsies, thymidylate synthase enzyme activity, a marker for DNA synthesis, had a circadian variation with peak activity in early afternoon, coinciding with the timing of S phase in our previous study on cell-cycle timing in human oral mucosa, The major peak in hPer1 expression occurs at the same time of day as the peak in G(1) phase in oral mucosa, suggesting a possible link between the circadian clock and the mammalian cell cycle.