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Oxidative damage under As3+ and/or Cu2+ stress leads to apoptosis and autophagy and may be cross-talking with mitochondrial disorders in bursa of Fabricius.
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.jinorgbio.2019.110989 Menghao Guo 1 , Yu Wang 1 , Hongjing Zhao 1 , Mengyao Mu 1 , Xin Yang 1 , Dongxue Fei 1 , Yachen Liu 1 , Hui Zong 2 , Mingwei Xing 1
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.jinorgbio.2019.110989 Menghao Guo 1 , Yu Wang 1 , Hongjing Zhao 1 , Mengyao Mu 1 , Xin Yang 1 , Dongxue Fei 1 , Yachen Liu 1 , Hui Zong 2 , Mingwei Xing 1
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Arsenic (As) exists in many forms in the whole natural environment, with As3+ the highest toxicity. Herein our study demonstrated that arsenic trioxide (As2O3) at a dose of 30 mg/kg caused serious oxidative damage to chickens' bursa of Fabricius (BF) in a time-dependent manner. Copper (Cu) is a necessary micronutrient and a key catalytic cofactor of many enzymes. We found excessive Cu (in the form of 300 mg/kg copper sulfate (CuSO4)) also induced severe oxidative stress (OxS), and its co-exposure with As3+ had a greater destructive power against oxidative system. Under electron microscope, swollen mitochondria, disappeared cristae and agglutinated chromatin were observed, accompanied by myeloid structure and autophagosome. The results showed apoptosis and autophagy occurred under the action of As3+ and Cu2+, and the situation was more serious in combined exposure group, which was further explained by terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine 5'-Triphosphate (dUTP) Nick-End Labeling (TUNEL). By quantitative real time polymerase chain reaction (RT-qPCR) and western blot, we found that mitochondrial dynamics were disordered under OxS, and the abnormal changes of B-cell lymphoma (Bcl)-2, p53, Bcl-2-interacting protein (Beclin)-1 and autophagy-related gene (ATG) 4B indicated the crosstalk between apoptosis and autophagy. In conclusion, apoptosis and autophagy of BF induced by As3+ and Cu2+ and mitochondrial disorder are closely related to the collapse of antioxidant system, and their connections are inseparable. Our results provide a reference for environmental risk prevention and selection of poultry feed additives and pesticides to avoid the health risks caused by As3+ and Cu2+ exposure.
中文翻译：
As3 +和/或Cu2 +胁迫下的氧化损伤导致细胞凋亡和自噬，并且可能与法氏囊的线粒体疾病发生串扰。
砷（As）在整个自然环境中以多种形式存在，其中As3 +的毒性最高。在本文中，我们的研究表明，剂量为30 mg / kg的三氧化二砷（As2O3）对鸡的法氏囊（BF）的法氏囊具有严重的氧化损伤，并具有时间依赖性。铜（Cu）是必需的微量营养元素，并且是许多酶的关键催化辅助因子。我们发现过量的Cu（以300 mg / kg硫酸铜（CuSO4）的形式）也诱导了严重的氧化应激（OxS），并且其与As3 +的共同暴露对氧化系统具有更大的破坏力。电镜下可见线粒体肿胀，cr消失，染色质凝集，并伴有髓样结构和自噬体。结果表明在As3 +和Cu2 +的作用下发生了凋亡和自噬，联合暴露组的情况更为严重，这可以通过末端脱氧核苷酸转移酶（TdT）介导的2'-脱氧尿苷5'-三磷酸（dUTP）尼克末端标记（TUNEL）进一步解释。通过实时定量聚合酶链反应（RT-qPCR）和Western印迹，我们发现在OxS干扰下线粒体动力学紊乱，B细胞淋巴瘤（Bcl）-2，p53，Bcl-2相互作用蛋白的异常变化（ Beclin）-1和自噬相关基因（ATG）4B表明细胞凋亡与自噬之间存在串扰。综上所述，As3 +，Cu2 +和线粒体疾病引起的BF的凋亡和自噬与抗氧化系统的崩溃密切相关，两者之间的联系密不可分。
更新日期：2020-01-07
中文翻译：
As3 +和/或Cu2 +胁迫下的氧化损伤导致细胞凋亡和自噬，并且可能与法氏囊的线粒体疾病发生串扰。
砷（As）在整个自然环境中以多种形式存在，其中As3 +的毒性最高。在本文中，我们的研究表明，剂量为30 mg / kg的三氧化二砷（As2O3）对鸡的法氏囊（BF）的法氏囊具有严重的氧化损伤，并具有时间依赖性。铜（Cu）是必需的微量营养元素，并且是许多酶的关键催化辅助因子。我们发现过量的Cu（以300 mg / kg硫酸铜（CuSO4）的形式）也诱导了严重的氧化应激（OxS），并且其与As3 +的共同暴露对氧化系统具有更大的破坏力。电镜下可见线粒体肿胀，cr消失，染色质凝集，并伴有髓样结构和自噬体。结果表明在As3 +和Cu2 +的作用下发生了凋亡和自噬，联合暴露组的情况更为严重，这可以通过末端脱氧核苷酸转移酶（TdT）介导的2'-脱氧尿苷5'-三磷酸（dUTP）尼克末端标记（TUNEL）进一步解释。通过实时定量聚合酶链反应（RT-qPCR）和Western印迹，我们发现在OxS干扰下线粒体动力学紊乱，B细胞淋巴瘤（Bcl）-2，p53，Bcl-2相互作用蛋白的异常变化（ Beclin）-1和自噬相关基因（ATG）4B表明细胞凋亡与自噬之间存在串扰。综上所述，As3 +，Cu2 +和线粒体疾病引起的BF的凋亡和自噬与抗氧化系统的崩溃密切相关，两者之间的联系密不可分。
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