Peroxiredoxin 2 nuclear levels are regulated by circadian clock synchronization in human keratinocytes
Peroxiredoxin 2 nuclear levels are regulated by circadian clock synchronization in human keratinocytes
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DOI：
10.1016/j.biocel.2014.04.024
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Torrisi, Maria Rosaria
中科院分区：
文献类型：
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作者：
Avitabile, Daniele;Ranieri, Danilo;Torrisi, Maria Rosaria
昼夜节律是高度保守的时间跟踪系统，在系统和细胞水平上调节重要的生物过程。本研究旨在鉴定人角质形成细胞中昼夜节律调节的蛋白质及其生物学功能，以HaCaT角质形成细胞为研究对象，在恒温自由运行条件下分离细胞组分，进行蛋白质组学研究。生物信息学分析表明，分子钟夹带与调节细胞增殖、能量代谢、转录、翻译和氧化还原平衡的分子组分的变化有关。核水平的抗氧化酶过氧化物酶2（PRDX2）被发现有节奏地振荡超过两个完整的24小时长的周期。PRDX2的失活导致了过氧化物酶特异性过氧化物酶3（PRDX3）的上调，而过氧化物酶家族的所有其他成员保持不变。此外，PRDX2敲低增加了细胞内活性氧（ROS）水平，并损害了细胞周期进展和增殖。我们的工作首次表明PRDX2的核水平显示昼夜节律振荡，参与调节人角质形成细胞的氧化还原平衡。(C)2014爱思唯尔有限公司版权所有。
Circadian rhythms are highly conserved time tracking systems regulating important biological processes at both systemic and cellular levels. The present study was aimed to identify proteins and biological functions circadian regulated in human keratinocytes.HaCaT keratinocytes were entrained by temperature cycles, and a proteomic study was performed on cell fractions isolated under free running conditions at constant temperature. Bioinformatics analysis revealed that molecular clock entrainment was associated with changes in molecular components regulating cell proliferation, energy metabolism, transcription, translation and redox balance. Nuclear levels of the antioxidant enzyme Peroxiredoxin 2 (PRDX2) were found to oscillate rhythmically over two entire 24 h long cycles. Donwregulation of PRDX2 resulted in upregulation of the mitochondrion-specific Peroxiredoxin 3 (PRDX3), all other members of the Peroxiredoxin family remained unaltered. Furthermore, PRDX2 knockdown increased intracellular levels of reactive oxygen species (ROS) and impaired cell cycle progression and proliferation. HaCaT cells transduced with a scramble shRNA were used as control.Our work is the first to show that nuclear levels of PRDX2 display circadian oscillation participating in the regulation of human keratinocytes redox balance. (C) 2014 Elsevier Ltd. All rights reserved.