Cadmium and molybdenum co-induce pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells
Cadmium and molybdenum co-induce pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells
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DOI：
10.1016/j.envpol.2020.116403
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发表时间：
2021-03-01
影响因子：
8.9
通讯作者：
Hu, Guoliang
中科院分区：
文献类型：
--
作者：
Zhang, Caiying;Lin, Tianjin;Hu, Guoliang
镉（Cd）和过量的钼（Mo）对动物有害，但镉和钼对鸭的联合肾毒性机制仍不清楚。为探讨镉和钼联合作用对鸭肾小管上皮细胞ROS/PTEN/PI 3 K/AKT轴的影响，采用3CdSO（4）中心点8H（2）O（4.0 μ M），（NH 4）（6）Mo 7 O24中心点4 H（2）O（500.0 μ M）、MCC 950（10.0 μ M）、BHA（100.0 μ M）以及Cd + Mo或Cd + Mo + MCC 950或Cd + Mo + BHA联合处理12 h，探讨联合细胞毒性。结果表明，钼、镉非等毒性二元混合物的毒性表现出协同作用。Mo和/或Cd使ROS水平、PTEN mRNA和蛋白水平升高，PI 3 K、AKT和p-AKT表达水平降低。同时，Mo和/或Cd可上调ASC、NLRP 3、NEK 7、Caspase-1、GSDMA、GSDME、IL-18和IL-1 β mRNA水平和Caspase-1 p20、NLRP 3、ASC、GSDMD蛋白水平，增加热凋亡细胞百分率、LDH、NO、IL-18和IL-1 β释放以及相对电导率。NLRP 3抑制剂MCC 950和活性氧清除剂BHA可改善钼镉共暴露引起的上述变化。总的来说，我们的研究结果表明，钼和镉的组合协同引起氧化应激和触发焦凋亡通过ROS/PTEN/PI 3 K/AKT轴在鸭肾小管上皮细胞。(C)2020爱思唯尔有限公司保留所有权利。
Cadmium (Cd) and excess molybdenum (Mo) are harmful to animals, but the combined nephrotoxic mechanism of Cd and Mo in duck remains poorly elucidated. To assess joint effects of Cd and Mo on pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells, cells were cultured with 3CdSO(4)center dot 8H(2)O (4.0 mu M), (NH4)(6)Mo7O24 center dot 4H(2)O (500.0 mu M), MCC950 (10.0 mu M), BHA (100.0 mu M) and combination of Cd and Mo or Cd, Mo and MCC950 or Cd, Mo and BHA for 12 h, and the joint cytotoxicity was explored. The results manifested that toxicity of non-equitoxic binary mixtures of Mo and Cd exhibited synergic interaction. Mo or/and Cd elevated ROS level, PTEN mRNA and protein levels, and decreased PI3K, AKT and p-AKT expression levels. Simultaneously, Mo or/and Cd upregulated ASC, NLRP3, NEK7, Caspase-1, GSDMA, GSDME, IL-18 and IL-1 beta mRNA levels and Caspase-1 p20, NLRP3, ASC, GSDMD protein levels, increased the percentage of pyroptotic cells, LDH, NO, IL-18 and IL-1 beta releases as well as relative conductivity. Moreover, NLRP3 inhibitor MCC950 and ROS scavenger BHA could ameliorate the above changed factors induced by Mo and Cd co-exposure. Collectively, our results reveal that combination of Mo and Cd synergistically cause oxidative stress and trigger pyroptosis via ROS/PTEN/PI3K/AKT axis in duck tubular epithelial cells. (C) 2020 Elsevier Ltd. All rights reserved.