Posttranscriptional regulation of pineal melatonin synthesis in Octodon degus.
Posttranscriptional regulation of pineal melatonin synthesis in Octodon degus.
复制标题
DOI：
10.1111/j.1600-079x.2009.00690.x
复制
发表时间：
2009-08
影响因子：
10.3
通讯作者：
Borjigin J
中科院分区：
文献类型：
--
作者：
Lee SJ;Liu T;Chattoraj A;Zhang SL;Wang L;Lee TM;Wang MM;Borjigin J
小实验室动物提供了重要的信息褪黑激素的调节，但大多数这些生物体是夜间和调节褪黑激素合成的机制，从人类的分歧。例如，在所有的啮齿动物检查，褪黑激素分泌发生的时间滞后数小时后，黑暗的发病;此外，芳基烷基胺N-乙酰转移酶（AANAT），褪黑激素合成的关键酶，显示动态转录激活，特别是在夜间在所有啮齿动物研究的日期。另一方面，在有蹄类动物和灵长类动物（包括人类）中，褪黑激素的分泌在深夜立即发生，并受AANAT的昼夜转录后调节控制。我们假设，昼夜活动的Hystricognath啮齿类动物的Dendon degus（）可以作为一个改进的实验模型，研究人类褪黑激素的调节。为了测试这一点，我们监测褪黑激素的生产在degus使用松果体微透析和特点的褪黑激素合成的调节分析degu Aanat。与有蹄类动物和灵长类动物一样，松果体褪黑激素在夜间几乎没有潜伏期。此外，degu Aanat mRNA的表达显示没有检测到的昼夜变化，这表明，像有蹄类动物和灵长类动物，褪黑激素在这个物种是由转录后机制。与所有啮齿类动物AANAT相比，预测的氨基酸序列与有蹄类动物和灵长类动物AANAT在遗传学上更接近。这些数据表明，拟黑腹蛛可能为研究昼行性哺乳动物褪黑激素合成和分泌机制提供了一个理想的模型系统。
Small laboratory animals have provided significant information about melatonin regulation, yet most of these organisms are nocturnal and regulate melatonin synthesis by mechanisms that diverge from those of humans. For example, in all rodents examined, melatonin secretion occurs with a time lag of several hours after the onset of darkness; in addition, arylalkylamine N-acetyltransferase (AANAT), the key enzyme in melatonin synthesis, displays dynamic transcriptional activation specifically at night in all rodents studied to date. In ungulates and primates including humans, on the other hand, melatonin secretion occurs immediately during the early night and is controlled by circadian posttranscriptional regulation of AANAT. We hypothesize that the diurnal Octodon degus (an Hystricognath rodent) could serve as an improved experimental model for studies of human melatonin regulation. To test this, we monitored melatonin production in degus using pineal microdialysis and characterized the regulation of melatonin synthesis by analyzing degu Aanat. Degu pineal melatonin rises with little latency at night, as in ungulates and primates. In addition, degu Aanat mRNA expression displays no detectable diurnal variation, suggesting that, like ungulates and primates, melatonin in this species is regulated by a posttranscriptional mechanism. Compared with AANAT from all rodents examined to date, the predicted amino acid sequence of degu AANAT is phylogenetically more closely related to ungulate and primate AANAT. These data suggest that Octodon degus may provide an ideal model system for laboratory investigation of mechanisms of melatonin synthesis and secretion in diurnal mammals.