Chen Menghao, Li Xiaojing, Fan Ruifeng, Yang Jie, Jin Xi, Hamid Sattar, Xu Shiwen
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
Chemosphere. 2018 Mar;194:396-402. doi: 10.1016/j.chemosphere.2017.12.026. Epub 2017 Dec 6.
Cadmium (Cd), a widespread environmental pollutant, has toxic effects on organs including spleen. However, the underlying mechanisms of Cd induced spleen toxicity and the roles of micro-RNA (miRNA) in this process remain poorly understood. To investigate this, cadmium chloride (CdCl, 10 mg/kg) was administered in the diet of chickens for 90 days. Electron microscopy, qPCR and Western blot were performed. Results showed that Cd exposure suppressed miR-33-5q which increased the levels of AMPK. Subsequently, significant decrease in AKT/mTOR signaling and HSP70 were observed. Concurrently, levels of NF-κB, p-JNK/JNK increased significantly. Moreover, the expression of BNIP3 and other autophagy markers (LC3-I, LC3-II, Beclin-1) increased significantly. Additionally, the levels of ions (Ca, Cr, Se, Sr, Sn, Ba) and (Na, Mg, V, Fe, Mo, Cu, Zn, Cd) significantly decreased and increased, respectively. Taken together, we conclude that Cd induced the deregulation of miR-33-AMPK axis led to BNIP3-dependent autophagy in chicken spleen through AKT/mTOR and HSP70-NF-κB/JNK signal pathways. In-addition Cd could affect ion homeostasis in chicken spleen.
镉（Cd）是一种广泛存在的环境污染物，对包括脾脏在内的器官具有毒性作用。然而，Cd诱导脾脏毒性的潜在机制以及微小RNA（miRNA）在此过程中的作用仍知之甚少。为了对此进行研究，将氯化镉（CdCl，10毫克/千克）添加到鸡的饲料中，持续90天。进行了电子显微镜检查、定量聚合酶链反应（qPCR）和蛋白质免疫印迹法。结果显示，Cd暴露抑制了miR-33-5q，从而增加了AMPK的水平。随后，观察到AKT/mTOR信号传导和热休克蛋白70（HSP70）显著降低。同时，核因子κB（NF-κB）、磷酸化c-Jun氨基末端激酶/ c-Jun氨基末端激酶（p-JNK/JNK）的水平显著升高。此外，BNIP3和其他自噬标志物（微管相关蛋白1轻链3-I，微管相关蛋白1轻链3-II，Beclin-1）的表达显著增加。另外，离子（钙、铬、硒、锶、锡、钡）和（钠、镁、钒、铁、钼、铜、锌、镉）的水平分别显著降低和升高。综上所述，我们得出结论，Cd诱导的miR-33-AMPK轴失调通过AKT/mTOR和HSP70-NF-κB/JNK信号通路导致鸡脾脏中BNIP3依赖的自噬。此外，Cd会影响鸡脾脏中的离子稳态。
