Post-self-repair process of neuron cells under the influence of neutral and cationic nanoparticles  

作　　者：Ting Wang Guanwen Qu Yu Deng Jing Shang Zhangqi Feng Fengyu Yang Nongyue He Jie Zheng 

机构地区：[1]State Key Laboratory of Bioelectronics,National Demonstration Centre for Experimental Biomedical Engineering Education,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210096,China [2]State Key Laboratory of Natural Medicines,Department of Pharmacology,China Pharmaceutical University,Nanjing 210002,China [3]Department of Chemical and Biomolecular Engineering,The University of Akron,OH 44325,United States [4]School of Chemical Engineering,Nanjing University of Science and Technology,Nanjing 210094,China [5]Nanjing Daniel New Mstar Technology Ltd.Nanjing 2U200,China

出　　处：《Chinese Chemical Letters》2019年第12期2368-2374,共7页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Nos.11204033,51773093);the Natural Science Foundation of Jiangsu Province (No.BK20141397);the Research Fund for the Doctoral Program of Higher Education of China (No.20120092120042);the CMA L’Oreal China Skin Grant 2015 (No.S2015121421);the Open Research Fund of State Key Laboratory of Natural Medicines,China Pharmaceutical University (No.SKLNMKF201803);Southeast University and Nanjing MedicalUniversity Cooperation Project (No.2242018K3DN14)

摘　　要：The prevalence of functionalized nanoparticles in biological and clinical fields attracts intensive toxicology investigations.Minimizing the nanoparticles’ biohazard remains a challenge due to the insufficient understanding on the nanoparticle-induced cell death mechanism.In the presented study,we observed the lysosome and genome injuries and so caused cell cycle changes and regulations of retinal ganglion neuron cell 5(RGC-5) induced by aminated and alkylated nanoparticles.Alkylated nanoparticles induced malignant lysosome and genome damages followed by severe post-self-repair responses.RGC-5 treated with alkylated nanoparticles presented dramatic S phase prolongation resulted from cyclin E accumulation mediated by Fbw7 downregulation,which assisted DNA replication after failed self-repair of the malignantly damaged DNA caused by alkylated nanoparticles.Differently,aminated nanoparticles in RGC-5 induced moderate lysosome and genome injuries and these damages could be repaired in the p21-involved pathway,so that cells did not induce apparent cyclin E accumulation nor Fbw7 downregulation as post-self-repair response.These results helped us to understand the toxicity of analogous nanoparticles on retinal ganglions such as glaucoma treatment.This work provides new insights into nanoparticle functionalization and toxicity in relation to the research on the toxicology and pathology of nerve cells.The prevalence of functionalized nanoparticles in biological and clinical fields attracts intensive toxicology investigations.Minimizing the nanoparticles’ biohazard remains a challenge due to the insufficient understanding on the nanoparticle-induced cell death mechanism.In the presented study,we observed the lysosome and genome injuries and so caused cell cycle changes and regulations of retinal ganglion neuron cell 5(RGC-5) induced by aminated and alkylated nanoparticles.Alkylated nanoparticles induced malignant lysosome and genome damages followed by severe post-self-repair responses.RGC-5 treated with alkylated nanoparticles presented dramatic S phase prolongation resulted from cyclin E accumulation mediated by Fbw7 downregulation,which assisted DNA replication after failed self-repair of the malignantly damaged DNA caused by alkylated nanoparticles.Differently,aminated nanoparticles in RGC-5 induced moderate lysosome and genome injuries and these damages could be repaired in the p21-involved pathway,so that cells did not induce apparent cyclin E accumulation nor Fbw7 downregulation as post-self-repair response.These results helped us to understand the toxicity of analogous nanoparticles on retinal ganglions such as glaucoma treatment.This work provides new insights into nanoparticle functionalization and toxicity in relation to the research on the toxicology and pathology of nerve cells.

关 键 词：LYSOSOME S phase Cyclin E P21 Fbw7 

分 类 号：R99[医药卫生—毒理学] TB383.1[医药卫生—药学]