Neurobiology and Molecular Chronobiology Laboratory, Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India.
Biogerontology. 2019 Aug;20(4):515-532. doi: 10.1007/s10522-019-09813-6. Epub 2019 May 16.
Suprachiasmatic nucleus (SCN) contains the central clock that orchestrate circadian rhythms in physiology and behavior in mammals. Tightly interlocked transcriptional and translational feedback loops (TTFLs) comprising of various clock genes such as Clock, Bmal1, Periods, Cryptochromes etc. in the SCN, send the timing signals to peripheral clocks that governs local metabolism with similar TTFLs. Peripheral clocks in kidney regulates several circadian rhythms like blood pressure, immunity etc. However, aging leads to circadian and inflammatory disorders in kidney. Though there are increasing evidences on age associated perturbations, studies elucidating the rhythmic expression of clock and immune genes across aging in kidney are obscure. We therefore studied changes in daily rhythms of clock and immune genes in kidney. In this study we measured mRNA expression of clock genes rBmal1, rPer1, rPer2, rCry1, rCry2, rRev-erbα, rRorα, and inflammatory genes rNfκb1, rTnfα, rIl6, rTlr4 and rTlr9 in 3, 12 and 24 months male Wistar rat kidney using qRT-PCR. From our study, we did not observe significant changes in clock genes expression except rRorα, but immune genes showed significant phase alterations as well as increase in mean 24 h levels. Pearson correlation analysis of data showed desynchronization between immune and clock genes expression. We further studied the effect of administration of curcumin which has anti-aging, anti-inflammatory, anti-oxidant etc. properties, and evaluated its chronobiotic properties. We here report differential effects of curcumin administration on daily rhythms of clock and immune genes expression.
视交叉上核（SCN）包含中央时钟，协调哺乳动物生理和行为的昼夜节律。SCN 中的各种时钟基因，如 Clock、Bmal1、Periods、Cryptochromes 等，组成了紧密相互作用的转录和翻译反馈环（TTFL），向调节局部代谢的外周时钟发送定时信号，这些时钟具有相似的 TTFL。肾脏中的外周时钟调节着几种昼夜节律，如血压、免疫等。然而，衰老会导致肾脏的昼夜节律和炎症紊乱。尽管有越来越多的证据表明与年龄相关的波动，但阐明肾脏中时钟和免疫基因随年龄变化的节律表达的研究仍不清楚。因此，我们研究了肾脏中时钟和免疫基因的日常节律变化。在这项研究中，我们使用 qRT-PCR 测量了 3、12 和 24 个月雄性 Wistar 大鼠肾脏中时钟基因 rBmal1、rPer1、rPer2、rCry1、rCry2、rRev-erbα、rRorα 和炎症基因 rNfκb1、rTnfα、rIl6、rTlr4 和 rTlr9 的 mRNA 表达。我们的研究结果表明，除了 rRorα 之外，时钟基因的表达没有明显变化，但免疫基因的相位变化以及 24 小时平均水平显著增加。数据的 Pearson 相关分析显示，免疫和时钟基因表达之间存在去同步。我们进一步研究了姜黄素的给药效果，姜黄素具有抗衰老、抗炎、抗氧化等特性，并评估了其生物钟特性。我们在此报告了姜黄素给药对时钟和免疫基因表达的日常节律的差异影响。
