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氨吸入介导的 mir-202-5p 通过 PTEN/AKT/mTOR 通路导致心脏自噬。

Ammonia inhalation-mediated mir-202-5p leads to cardiac autophagy through PTEN/AKT/mTOR pathway.

机构信息

College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

出版信息

Chemosphere. 2019 Nov;235:858-866. doi: 10.1016/j.chemosphere.2019.06.235. Epub 2019 Jul 1.

Abstract

Ammonia is a known environmental pollutant around the world. It leads to the deterioration of air quality and has adverse effects on human health. Although previous studies have demonstrated that ammonia caused some health problems to chickens, it is still unclear whether ammonia causes cardiac toxicity. The functional autophagy is very important for cardiac homeostasis. Therefore, the role of autophagy was investigated in the mechanism of chicken heart damage induced by environmental contaminant ammonia in our present study. The results from the oxidative stress index (SOD, GPx, HO, and MDA), NO content, iNOS activity, and transmission electron microscopy indicated that excess ammonia induced oxidative stress and autophagy in the chicken heart. The expression results from miR-202-5p and PTEN/AKT/mTOR (PTEN, LC3-I, LC3-II, p-AKT, AKT, Beclin1, Dynein, ATG5, p-mTOR and mTOR) signaling pathway-related genes further confirmed that excess ammonia induced cardiac autophagy. In conclusion, these results demonstrated that excess ammonia can cause cardiac damage and mediate mir-202-5p to regulate autophagy through PTEN/AKT/mTOR pathway in the chicken heart injury. Our findings will provide a new insight for better assessing the toxicity mechanism of environmental pollutants ammonia on the heart.

摘要

氨是一种在全球范围内已知的环境污染物。它会导致空气质量恶化,并对人类健康产生不利影响。尽管之前的研究表明氨会对鸡造成一些健康问题,但仍不清楚氨是否会导致心脏毒性。功能自噬对于心脏内稳态非常重要。因此,在本研究中,我们研究了环境污染物氨诱导鸡心脏损伤的机制中自噬的作用。氧化应激指标(SOD、GPx、HO 和 MDA)、NO 含量、iNOS 活性和透射电子显微镜的结果表明,过量的氨会在鸡心中诱导氧化应激和自噬。miR-202-5p 和 PTEN/AKT/mTOR(PTEN、LC3-I、LC3-II、p-AKT、AKT、Beclin1、Dynein、ATG5、p-mTOR 和 mTOR)信号通路相关基因的表达结果进一步证实,过量的氨会诱导心脏自噬。总之,这些结果表明,过量的氨会导致心脏损伤,并通过鸡心中的 PTEN/AKT/mTOR 通路介导 mir-202-5p 调节自噬。我们的研究结果将为更好地评估环境污染物氨对心脏的毒性机制提供新的见解。

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