PMID- 30090396
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240415
IS  - 2045-452X (Print)
IS  - 2045-4538 (Electronic)
IS  - 2045-452X (Linking)
VI  - 5
IP  - 3
DP  - 2016 May 1
TI  - Autophagy and autophagy dysfunction contribute to apoptosis in HepG2 cells 
      exposed to nanosilica.
PG  - 871-882
LID - 10.1039/c5tx00465a [doi]
AB  - Great concerns have led to the evaluation of the potential hazards of nanosilica 
      to human health and the environment. However, there still exists persistent 
      debates on the biological effects and toxic consequences induced by nanosilica. 
      The present study investigated both autophagy and apoptosis in ICR mice and Human 
      hepatocellular carcinoma cells (HepG2), and then explored the interactive 
      mechanism between these two distinct cell death modalities in HepG2 cells. Mice 
      liver injuries seen by hematoxylin and eosin (HE) staining indicated the 
      hepatotoxic effects of nanosilica. The TUNEL assay and immunohistochemistry 
      results confirmed that nanosilica could induce both apoptosis and autophagy in 
      vivo. Flow cytometry analysis demonstrated apoptosis induction in vitro, while 
      autophagic ultrastructures, LC3-II expression and immunofluorescence clarified 
      autophagy activation by nanosilica. Apoptosis suppression by the autophagy 
      inhibitor of 3-methyladenine (3-MA) implied that autophagy was involved in 
      apoptotic cell death. A mechanistic study verified that nanosilica induced 
      autophagy via negative regulation of mammalian target of rapamycin (mTOR) 
      signaling but not the Beclin-1 associated pathway. The enhancement of p62 
      accumulation and mTOR down-regulation might account for the molecular mechanism 
      in contribution of autophagy to apoptosis. As an emerging new mechanism of 
      nanomaterial toxicity, autophagy might be a more susceptive indicator for 
      toxicological consequence evaluation in nanoparticle toxicity. The present study 
      provides novel evidence to elucidate the toxicity mechanisms and may be 
      beneficial to more rational applications of nanosilica in the future.
FAU - Yu, Yongbo
AU  - Yu Y
AD  - Beijing Key Laboratory for Pediatric Diseases of Otolaryngology , Head and Neck 
      Surgery , Beijing Pediatric Research Institute , Beijing Children's Hospital , 
      Capital Medical University , Beijing , P.R. China.
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
FAU - Duan, Junchao
AU  - Duan J
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
FAU - Yu, Yang
AU  - Yu Y
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
FAU - Li, Yang
AU  - Li Y
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
FAU - Zou, Yang
AU  - Zou Y
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
FAU - Yang, Yumei
AU  - Yang Y
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
FAU - Jiang, Lizhen
AU  - Jiang L
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
FAU - Li, Qiuling
AU  - Li Q
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
FAU - Sun, Zhiwei
AU  - Sun Z
AD  - School of Public Health , Capital Medical University , Beijing , 100069 , P.R. 
      China . Email: zwsun@ccmu.edu.cn ; ; Tel: +86 010 83911507.
AD  - Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , 
      Beijing , 100069 , P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160308
PL  - England
TA  - Toxicol Res (Camb)
JT  - Toxicology research
JID - 101587950
EIN - Toxicol Res (Camb). 2023 Sep 13;12(5):1005. PMID: 38617085
PMC - PMC6062368
EDAT- 2016/03/08 00:00
MHDA- 2016/03/08 00:01
PMCR- 2017/03/08
CRDT- 2018/08/10 06:00
PHST- 2015/12/10 00:00 [received]
PHST- 2016/02/28 00:00 [accepted]
PHST- 2018/08/10 06:00 [entrez]
PHST- 2016/03/08 00:00 [pubmed]
PHST- 2016/03/08 00:01 [medline]
PHST- 2017/03/08 00:00 [pmc-release]
AID - c5tx00465a [pii]
AID - 10.1039/c5tx00465a [doi]
PST - epublish
SO  - Toxicol Res (Camb). 2016 Mar 8;5(3):871-882. doi: 10.1039/c5tx00465a. eCollection 
      2016 May 1.