Abstract：
Our previous study showed that sodium arsenite (200 mg/L) affected the nervous system and induced motor neuron development via the Sonic hedgehog pathway in zebrafish larvae. To gain more insight into the effects of arsenite on other signaling pathways, including apoptosis, we have performed quantitative polymerase chain reaction array-based gene expression analyses. The 96-well array plates contained primers for 84 genes representing 10 signaling pathways that regulate several biological functions, including apoptosis. We exposed eggs at 5 h postfertilization until the 72 h postfertilization larval stage to 200 mg/L sodium arsenite. In the Janus kinase/signal transducers and activators of transcription, nuclear factor κ-light-chain-enhancer of activated B cells, and Wingless/Int-1 signaling pathways, the expression of only one gene in each pathway was significantly altered. The expression of multiple genes was altered in the p53 and oxidative stress pathways. Sodium arsenite induced excessive apoptosis in the larvae. This compelled us to analyze specific genes in the p53 pathway, including cdkn1a, gadd45aa, and gadd45ba. Our data suggest that the p53 pathway is likely responsible for sodium arsenite-induced apoptosis. In addition, sodium arsenite significantly reduced global DNA methylation in the zebrafish larvae, which may indicate that epigenetic factors could be dysregulated after arsenic exposure. Together, these data elucidate potential mechanisms of arsenic toxicity that could improve understanding of arsenic\'s effects on human health.
摘要：
我们先前的研究表明，亚砷酸钠（200mg/L）通过Sonichedgehog途径影响斑马鱼幼虫的神经系统并诱导运动神经元发育。为了更深入地了解亚砷酸盐对其他信号通路的影响，包括细胞凋亡,我们进行了基于定量聚合酶链反应阵列的基因表达分析.96孔阵列板包含84个基因的引物，这些基因代表了10个调节几种生物学功能的信号通路，包括细胞凋亡。我们在受精后5小时将卵暴露于200mg/L亚砷酸钠，直到受精后72小时幼虫阶段。在Janus激酶/信号转导和转录激活因子中，活化B细胞的核因子κ轻链增强子,和无翼/Int-1信号通路，每个途径中只有一个基因的表达发生了显著改变。p53和氧化应激途径中多个基因的表达发生了改变。亚砷酸钠诱导幼虫过度凋亡。这迫使我们分析p53通路中的特定基因，包括cdkn1a,gadd45aa,和gadd45ba。我们的数据表明p53途径可能是亚砷酸钠诱导的细胞凋亡的原因。此外,亚砷酸钠显著降低了斑马鱼幼虫的DNA甲基化，这可能表明砷暴露后表观遗传因素可能失调。一起,这些数据阐明了砷毒性的潜在机制，可以提高人们对砷对人类健康影响的认识。
