College of Wildlife Resources, Northeast Forestry University, Harbin 150040, People's Republic of China.
College of Wildlife Resources, Northeast Forestry University, Harbin 150040, People's Republic of China.
Ecotoxicol Environ Saf. 2018 Feb;148:125-134. doi: 10.1016/j.ecoenv.2017.10.018. Epub 2017 Nov 6.
Basal autophagy has an indispensable role in the functioning and maintenance of cardiac geometry under physiological conditions. Recently, increasing evidence has demonstrated that arsenic (As)/copper (Cu) play important roles in the autophagy of the heart. The current study was to evaluate whether oxidative damage by As or/and Cu was correlated with autophagy through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in the heart of birds. Arsenic trioxide (30mg/kg) or/and cupric sulfate (300mg/kg) were administered in a basal diet to male Hy-line chickens (one-day-old) for 12 weeks. The results showed that heart weight/body weight ratio decreased in the As + Cu group only at 4, 8 and 12 weeks. Moreover, we observed that As or/and Cu decreased high-density lipoprotein cholesterol (HDL-C) concentrations, increased total cholesterol (T-CHO) concentrations and cardiac enzymes activities in the serum. On the other hand, As or/and Cu significantly reduced the activities of total antioxidant (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)) along with decreased nonenzymic antioxidant (glutathione (GSH)) concentrations and increased malondialdehyde (MDA) concentrations in the heart. Furthermore, As or/and Cu could induce autophagy in the heart of chickens through decreased mRNA levels of TORC1, TORC2, microtubule associated light chains 3-I (LC3-I) and increased PI3K, AKT1, Beclin1, autophagy associated gene 4B (Atg4B), microtubule associated light chains 3-II (LC3-II), autophagy associated gene 5 (Atg5) and Dynein. Meanwhile, ultrastructural examinations showed that As/Cu could result in the appearance of autolygosomes, autophagic vacuoles and double-membrane structures in the heart. In conclusion, As or/and Cu induced cardiac damage and autophagy via elevating cardiac enzymes activities, inducing oxidative stress and activating the PI3K/AKT/mTORC pathway in heart of chickens. Moreover, As and Cu had a possible synergistic relationship in the heart of chickens.
基础自噬在生理条件下心脏形态和功能的维持中起着不可或缺的作用。最近，越来越多的证据表明砷（As）/铜（Cu）在心脏自噬中起重要作用。本研究旨在评估砷或/和铜通过心脏中的磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/雷帕霉素靶蛋白（mTOR）通路引起的氧化损伤是否与自噬有关。三氧化二砷（30mg/kg）或/和硫酸铜（300mg/kg）添加到雄性海兰鸡（1 日龄）的基础日粮中，持续 12 周。结果显示，仅在 4、8 和 12 周时，砷加铜组的心脏重量/体重比下降。此外，我们观察到砷或/和铜降低了血清中高密度脂蛋白胆固醇（HDL-C）浓度，增加了总胆固醇（T-CHO）浓度和心脏酶活性。另一方面，砷或/和铜显著降低了总抗氧化（T-AOC）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）的活性，同时降低了非酶抗氧化剂（谷胱甘肽（GSH））浓度，增加了心脏中的丙二醛（MDA）浓度。此外，砷或/和铜可以通过降低 TORC1、TORC2、微管相关轻链 3-I（LC3-I）的 mRNA 水平，增加 PI3K、AKT1、Beclin1、自噬相关基因 4B（Atg4B）、微管相关轻链 3-II（LC3-II）、自噬相关基因 5（Atg5）和动力蛋白来诱导鸡心脏中的自噬。同时，超微结构检查显示，砷/铜可导致心脏自噬溶酶体、自噬空泡和双膜结构的出现。总之，砷或/和铜通过提高心脏酶活性、诱导氧化应激和激活鸡心脏中的 PI3K/AKT/mTORC 通路，诱导心脏损伤和自噬。此外，砷和铜在鸡心脏中可能存在协同关系。
