Bjarnason G A, Jordan R C, Wood P A, Li Q, Lincoln D W, Sothern R B, Hrushesky W J, Ben-David Y
Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada.
Am J Pathol. 2001 May;158(5):1793-801. doi: 10.1016/S0002-9440(10)64135-1.
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 in 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.
我们在一天24小时内，对8名健康的日间活动男性研究参与者口腔黏膜和皮肤活检样本中生物钟基因的相对RNA表达进行了研究。我们发现，人类生物钟基因hClock、hTim、hPer1、hCry1和hBmal1在口腔黏膜和皮肤中均有表达，其昼夜节律模式与在啮齿动物视交叉上核及外周组织中发现的一致。hPer1、hCry1和hBmal1呈现节律性表达，分别在清晨、傍晚和夜间达到峰值，而hClock和hTim则无节律性。这是首次在人类研究中显示出如啮齿动物中所记录的所有五个生物钟基因的昼夜表达模式，表明它们在人类中具有重要功能。在同时进行的口腔黏膜活检中，作为DNA合成标志物的胸苷酸合成酶活性呈现昼夜变化，在下午早些时候达到活性峰值，这与我们之前关于人类口腔黏膜细胞周期时间的研究中S期的时间一致。hPer1表达的主要峰值出现在与口腔黏膜G(1)期峰值相同的时间，这表明生物钟与哺乳动物细胞周期之间可能存在联系。
