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首页> 外文期刊>Journal of biochemical and molecular toxicology >Excess hydrogen peroxide inhibits head and foot regeneration in hydra by affecting DNA repair and expression of essential genes
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Excess hydrogen peroxide inhibits head and foot regeneration in hydra by affecting DNA repair and expression of essential genes

机译：过量过氧化氢通过影响DNA修复和必需基因的表达来抑制Hydra的头部和足部再生

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摘要

Reactive oxygen species (ROS) are necessary for various cellular processes. However, excess ROS cause damage to many biological molecules and therefore must be tightly regulated in time and space. Hydrogen peroxide (H_2O_2) is the most commonly used ROS as second messenger in the cell. It is a relatively long-lived freely diffusible signaling molecule during early events of injury. In the Cnidarian hydra, injury-induced ROS production is essential for regeneration to proceed. In the present study, we have examined influence of varying exposure to H_2O_2 on head and foot regeneration in the middlepieces of trisected hydra. We find that longer (4 hours) exposure to 1 mM H_2O_2 inhibits both head and foot regeneration while shorter exposure (2 hours) does not. Longer exposure to H_2O_2 resulted in extensive damage to DNA that could not be repaired, probably due to suboptimal induction of APE1, an enzyme necessary for base excision repair (BER). Concomitantly, genes involved in activation of Wnt pathway, necessary for head regeneration, were significantly downregulated. This appeared to be due to failure of both stabilization and transient nuclear localization of β-catenin. Similarly, genes involved in foot regeneration were also downregulated on longer exposure to H_2O_2. Thus, exposure to excess ROS inhibits regenerative processes in hydra through reduced expression of genes involved in regeneration and diminished DNA repair.
机译：活性氧（ROS）是各种细胞过程所必需的。然而，过量的活性氧会对许多生物分子造成损害，因此必须在时间和空间上进行严格的调控。过氧化氢（H_2O_2）是细胞中最常用的第二信使活性氧。在损伤早期，它是一种相对长寿命的自由扩散信号分子。在蛇形纲水螅中，损伤诱导的活性氧生成对再生的进行至关重要。在本研究中，我们研究了不同暴露于H_2O_2对三等分水螅中段头和脚再生的影响。我们发现，长时间（4小时）暴露在1毫米H_2O_2中会抑制头和脚的再生，而短时间（2小时）则不会。长时间接触H_2O_2会导致无法修复的DNA广泛损伤，这可能是由于APE1（碱基切除修复（BER）所需的一种酶）的诱导不理想所致。同时，参与Wnt通路激活的基因（头部再生所必需的）显著下调。这似乎是由于β-连环蛋白的稳定和瞬时核定位失败所致。类似地，脚部再生相关基因在长时间接触H_2O_2后也会下调。因此，暴露于过量的ROS会通过减少再生相关基因的表达和减少DNA修复来抑制hydra的再生过程。

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