ROS-Drp1-mediated mitochondria fission contributes to hippocampal HT22 cell apoptosis induced by silver nanoparticles

被引：66

作者：

Chang, Xiaoru ^{[1
]}

Niu, Shuyan ^{[1
]}

Shang, Mengting ^{[1
]}

Li, Jiangyan ^{[1
]}

Guo, Menghao ^{[1
]}

Zhang, Wenli ^{[1
]}

Sun, Zuoyi ^{[1
]}

Li, Yunjing ^{[1
]}

Zhang, Rui ^{[1
]}

Shen, Xin ^{[1
]}

Tang, Meng ^{[1
]}

Xue, Yuying ^{[1
]}

机构：

[1] Southeast Univ, Sch Publ Hlth, Key Lab Environm Med & Engn, Minist Educ, Nanjing 210009, Peoples R China

来源：

REDOX BIOLOGY | 2023年 / 63卷

关键词：

Silver nanoparticles; Neurotoxicity; Mitochondrial fission; Drp1; Apoptosis; TIO2; NANOPARTICLES; DYSFUNCTION;

D O I：

10.1016/j.redox.2023.102739

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Silver nanoparticles (AgNPs) have widely used in industrial and medical applications for their excellent anti-bacterial activities. AgNPs can penetrate into the brain and cause neuronal death, but limited evidence focused on toxic effects and mechanic study in hippocampal neuron. This study aimed to investigate the molecular mechanisms of mitochondrial damage and apoptosis in mouse hippocampal HT22 cells and further to explore role of reactive oxygen species (ROS) and GTPase dynamin-related protein 1 (Drp1) in AgNPs-induced neuro-toxicity. Our results showed that acute exposure to AgNPs at low doses (2-8 mu g/mL) increased ROS generation, decreased mitochondrial membrane potential (MMP) and ATP synthesis in HT22 cells. In addition, AgNPs promoted mitochondrial fragmentation and mitochondria-dependent apoptosis via excessive mitochondrial fission/fusion by 8 mu g/mL AgNPs treatment for 24 h. The mechanism was involved in increased protein expression of Drp1, mitochondrial fission protein 1 (Fis1), mitofusin 1/2 (Mfn1/2) and inhibited optic atrophy 1 (OPA1), and mainly mediated by phosphorylation of Drp1 Ser616. The AgNPs-induced mitochondrial impair-ment and apoptosis was mainly due to their particle-specific effect rather than silver ions release. Furthermore Drp1-mediated mitochondrial fission contributed to mitochondria-dependent apoptosis induced by AgNPs, all aforementioned changes were significantly rescued by N-acetyl-L-cysteine (NAC) and Mdivi-1 except for OPA1 protein expression. Hence, our results provide a novel neurotoxic mechanism to AgNPs-induced neurotoxicity and revealed that the mechanism of mitochondria-dependent apoptosis in HT22 cells was mediated by excessive activation of ROS-Drp1-mitochondrial fission axis. These findings can deepen current evidences on neuro-toxicological evaluation of AgNPs and aid in guiding their proper applications in different areas, especially in biomedical use.

引用

页数：13

共 31 条

[1] Silver nanoparticles induced hippocampal neuronal damage involved in mitophagy, mitochondrial biogenesis and synaptic degeneration [J].