title: Graphene oxide quantum dots disrupt autophagic flux by inhibiting lysosome activity in GC-2 and TM4 cell lines.
abstract: Graphene oxide quantum dots (GOQDs) have broad application prospects in many areas including bioimaging, drug delivery, DNA cleavage system, sensors and photocatalyst. Recently, increasing concerns have been raised about their biocompatibility, but studies about the effects of GOQDs on male reproductive system are still lacking. In this work, we explored the effects and molecular mechanisms of GOQDs on GC-2 and TM4 cells. We found autophagosome accumulation in GC-2 and TM4 cells after GOQDs treatment. Both LC3-II/LC3-I ratio and p62 levels increased, and the chloroquine-induced accumulation of LC3-II didn't enhance in the presence of GOQDs, which indicated that GOQDs blocked autophagic flux. Further studies found that the fusion between autophagosome and lysosome was not inhibited by GOQDs, but the proteolytic capacity of lysosome was weakened and both the expression and activity of cathepsin B reduced. Taken together, these results suggested that GOQDs blocked autophagic flux by decreasing the amount and enzymatic activity of cathepsin B and inhibiting lysosome proteolytic capacity in GC-2 and TM4 cells, which might have a potential hazard to male reproduction.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Changzhou Maternity and Child Health Care Hospital affiliated to Nanjing Medical University, Changzhou, Jiangsu 213003, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Xu
authors.affiliation: Medical School, Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Qiusha
authors.initials: Q
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: yankaixia@njmu.edu.cn.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002401:Cathepsin B / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D006108:Graphite / Q000633:toxicity*; D008247:Lysosomes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D045663:Quantum Dots / Q000633:toxicity*
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D016271:Proto-Oncogene Proteins c-myc; D006108:Graphite; D002738:Chloroquine; D000135:Acid Phosphatase; D002401:Cathepsin B; C533915:Ctsb protein, mouse
keywords: Autophagic flux; Cathepsin B; Graphene oxide quantum dots; Lysosome activity