本研究的主要目的是探讨砷暴露对子代不同发育阶段小鼠海马磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/核转录因子-κB(NF-κB)信号通路的影响。以0、15、30或60mg/L的剂量给予雌性小鼠及其幼仔亚砷酸钠(NaAsO2)。通过EMSA评估NF-κB的核易位水平。实时RT-PCR用于测量Akt,NF-κB和PI3KmRNA水平。PI3K的蛋白表达,p-Akt,抑制剂κB激酶(IKK),p-NF-κB,蛋白激酶A(PKA),抑制剂κB(IκB),蛋白质印迹法检测cAMP反应元件结合蛋白(CREB)。结果表明,暴露于60mg/LNaAsO2可以抑制出生后第(PND)20和PND40小鼠核易位的NF-κB水平。砷下调PI3K的转录和翻译水平,Akt和NF-κB。此外,p-IKK的蛋白表达,p-IκB,PKA和p-CREB也降低了。一起来看,结果表明,砷能够下调PI3K/Akt/NF-κB信号通路,特别是在PND40上,这可能与认知障碍有关。
The primary purpose of present study was to explore the effects of arsenic exposure on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (
Akt)/nuclear transcription factor-κB (NF-κB) signaling pathway in the hippocampus of offspring mice at different developmental stages. Sodium arsenite (NaAsO2) at doses of 0, 15, 30 or 60 mg/L administered to female mice and their pups. The nuclear translocation levels of NF-κB were assessed by EMSA. Real-time RT-PCR was used to measure
Akt, NF-κB and PI3K mRNA levels. Protein expressions of PI3K, p-
Akt, inhibitor kappa B kinase (IKK), p-NF-κB, protein kinase A (PKA), inhibitor kappa B (IκB), and cAMP response element-binding protein (CREB) were measured by Western blot. Results disclosed that exposure to 60 mg/L NaAsO2 could suppress NF-κB levels of nuclear translocation of postnatal day (PND) 20 and PND 40 mice. Arsenic downregulated the transcriptional and translational levels of PI3K,
Akt and NF-κB. Additionally, protein expressions of p-IKK, p-IκB, PKA and p-CREB also reduced. Taken together, results of present study indicated that arsenic could downregulate the PI3K/
Akt/NF-κB signaling pathway, particularly on PND 40, which might be involved in the cognitive impairments.