Institute of Three Gorges Ecological Fisheries of Chongqing, College of Fisheries, Southwest University, Chongqing 400715, China.
Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Southwest University, Chongqing 400715, China.
Genes (Basel). 2020 Sep 24;11(10):1118. doi: 10.3390/genes11101118.
Oxidation resistance gene 1 () is essential for protection against oxidative stress in mammals, but its functions in non-mammalian vertebrates, especially in fish, remain uncertain. Here, we created a homozygous -knockout zebrafish via the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9) system. Compared with wild-type (WT) zebrafish, mutants exhibited higher mortality and more apoptotic cells under oxidative stress, and multiple antioxidant genes (i.e., , , and ) involved in detoxifying cellular reactive oxygen species were downregulated significantly. Based on these observations, we conducted a comparative transcriptome analysis of early oxidative stress response. The results show that mutation caused more extensive changes in transcriptional networks compared to WT zebrafish, and several stress response and pro-inflammatory pathways in mutant zebrafish were strongly induced. More importantly, we only observed the activation of the p53 signaling and apoptosis pathway in mutant zebrafish, revealing an important role of in regulating apoptosis via the p53 signaling pathway. Additionally, we found that mutation displayed a shortened lifespan and premature ovarian failure in prolonged observation, which may be caused by the loss of impaired antioxidant defenses, thereby increasing pro-apoptotic events. Altogether, our findings demonstrate that is vital for antioxidant defenses and anti-aging in zebrafish.
氧化还原酶 1 () 是哺乳动物抵抗氧化应激的必需基因，但它在非哺乳动物脊椎动物（尤其是鱼类）中的功能尚不确定。在这里，我们通过 CRISPR/Cas9（Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9）系统创建了纯合的 - 基因敲除斑马鱼。与野生型（WT）斑马鱼相比， 突变体在氧化应激下表现出更高的死亡率和更多的凋亡细胞，并且参与细胞内活性氧解毒的多个抗氧化基因（即 、 、 和 ）显著下调。基于这些观察结果，我们对早期氧化应激反应进行了比较转录组分析。结果表明， 突变导致转录网络发生的变化比 WT 斑马鱼更为广泛，并且 突变斑马鱼中的几种应激反应和促炎途径被强烈诱导。更重要的是，我们仅在 突变斑马鱼中观察到 p53 信号和细胞凋亡途径的激活，表明 在通过 p53 信号通路调节细胞凋亡中起重要作用。此外，我们发现 突变在长时间观察中表现出寿命缩短和卵巢早衰，这可能是由于 缺失导致抗氧化防御受损，从而增加了促凋亡事件。总之，我们的研究结果表明， 在斑马鱼的抗氧化防御和抗衰老中至关重要。
