The Light-Inducible Genes Per2, Cry1a, and Cry2a Regulate Oxidative Status in Zebrafish
The Light-Inducible Genes Per2, Cry1a, and Cry2a Regulate Oxidative Status in Zebrafish
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DOI：
10.1248/bpb.b21-00432
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发表时间：
2021-08-01
影响因子：
2
通讯作者：
Nishina, Hiroshi
中科院分区：
文献类型：
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作者：
Alifu, Yikelamu;Kofuji, Satoshi;Nishina, Hiroshi
生物钟是一种高度保守的24小时生物振荡机制，受到光、食物和温度等环境刺激的影响。生物钟的紊乱会导致多种生物过程的紊乱，包括睡眠-觉醒周期和新陈代谢。虽然我们以前在斑马鱼中发现了生物钟的几个组成部分，但我们对光诱导时钟基因和新陈代谢之间的关系的理解仍然不完整。为了研究光诱导时钟基因如何调节新陈代谢，我们对斑马鱼的光诱导时钟基因zPer2、zCry1a和zCry2a进行了转录和代谢组学分析。对zPer2/zCry1a双基因敲除(DKO)和zPer2/zCry1a/zCry2a三基因敲除(TKO)突变体的转录转录分析表明，它们的基因表达谱与野生型(WT)斑马鱼不同。特别是，编码氧化应激感受器的zKeap1a的mRNA水平在DKO和TKO突变体中增加。代谢组学分析显示，代谢组谱发生了基因依赖性的改变。主成分分析和偏最小二乘判别分析显示半胱氨酸/蛋氨酸代谢和谷胱甘肽代谢的改变。具体地说，TKO斑马鱼的半胱氨酸和谷胱甘肽含量降低，蛋氨酸亚砜含量增加。这些结果表明，光诱导基因zPer2、zCry1a和zCry2a参与调节斑马鱼的氧化状态。
The circadian clock is a highly conserved 24 h biological oscillation mechanism and is affected by environmental stimuli such as light, food and temperature. Disruption of the circadian clock results in disorders of diverse biological processes, including the sleep-wake cycle and metabolism. Although we previously identified several components of the circadian clock in zebrafish, our understanding of the relationship between light-inducible clock genes and metabolism remains incomplete. To investigate how light-inducible clock genes regulate metabolism, we performed transcriptomic and metabolomic analyses of the light-inducible clock genes zPer2, zCry1a, and zCry2a in zebrafish. Transcriptomic analysis of zPer2/zCry1a double knockout (DKO) and zPer2/zCry1a/zCry2a triple knockout (TKO) mutants showed that their gene expression profiles differed from that of wild type (WT) zebrafish. In particular, mRNA levels of zKeap1a, which encodes an oxidative stress sensor, were increased in DKO and TKO mutants. Metabolomic analysis showed genotypedependent alteration of metabolomic profiles. Principal component analysis ( PCA) and partial least squaresdiscriminant analysis (PLS-DA) showed the alteration of cysteine/methionine metabolism and glutathione metabolism. Specifically, cysteine and glutathione were decreased but methionine sulfoxide was increased in TKO zebrafish. These results indicate that the light-inducible genes zPer2, zCry1a, and zCry2a are involved in regulating the oxidative status of zebrafish.