College of Veterinary Medicine, Sichuan Agricultural University, 211 Huimin Road, Chengdu, 611130, Sichuan, China.
College of Science, Sichuan Agricultural University, 211 Huimin Road, Chengdu, 611130, Sichuan, China.
Biol Trace Elem Res. 2021 Mar;199(3):1062-1073. doi: 10.1007/s12011-020-02212-w. Epub 2020 Jul 14.
Silver nanoparticles (AgNPs) are widely used in industrial products, and they have good antibacterial properties, with potential for prevention and treatment of cow mastitis. However, concerns exist about the cytotoxicity of AgNPs. Thus, we have studied the role of autophagy in AgNP-induced cytotoxicity in mouse HC11 mammary epithelium cells. We found that AgNPs injured HC11 cells, with release of lactate dehydrogenase (LDH). AgNPs also induced autophagy in HC11 cells, which was associated with oxidative stress, as indicated by increased reactive oxygen species (ROS) and increased expression of hemoxygenase-1(HO-1) and Nrf2. Mitochondria were altered by AgNPs: mitochondrial membrane potential (MMP) was decreased and the expression of PINK1 and Parkin was increased. AgNPs also increased the expression of p-AMPK and decreased the expression of p-Akt and p-mTOR. The addition of 3-methyl adenine inhibited autophagy and enhanced the cytotoxicity of AgNPs, indicating that autophagy is protective against AgNP-induced cell death. In summary, AgNPs induced protective autophagy in HC11 cells via the Akt/AMPK/mTOR pathway, associated with cellular oxidative stress and mitochondrial alterations. Our research confirms that AgNPs may damage the breast tissue in clinical applications and should be used with caution. Further research is necessary to clarify whether the damage caused by AgNPs will affect the lactation function of the mammary glands and possible residues in milk.
银纳米粒子（AgNPs）广泛应用于工业产品，具有良好的抗菌性能，有望预防和治疗奶牛乳腺炎。然而，人们对 AgNPs 的细胞毒性表示担忧。因此，我们研究了自噬在 AgNP 诱导的小鼠 HC11 乳腺上皮细胞细胞毒性中的作用。我们发现 AgNPs 损伤了 HC11 细胞，导致乳酸脱氢酶（LDH）释放。AgNPs 还诱导了 HC11 细胞的自噬，这与氧化应激有关，表现为活性氧（ROS）增加、血红素加氧酶-1（HO-1）和核因子红细胞 2（Nrf2）表达增加。AgNPs 改变了线粒体：线粒体膜电位（MMP）降低，PINK1 和 Parkin 的表达增加。AgNPs 还增加了 p-AMPK 的表达，降低了 p-Akt 和 p-mTOR 的表达。添加 3-甲基腺嘌呤抑制自噬并增强 AgNPs 的细胞毒性，表明自噬对 AgNP 诱导的细胞死亡具有保护作用。总之，AgNPs 通过 Akt/AMPK/mTOR 通路诱导 HC11 细胞保护性自噬，与细胞氧化应激和线粒体改变有关。我们的研究证实，AgNPs 在临床应用中可能会损害乳腺组织，应谨慎使用。需要进一步研究阐明 AgNPs 造成的损害是否会影响乳腺的泌乳功能以及牛奶中可能的残留。
