PMID- 35884757
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 2076-3425 (Print)
IS  - 2076-3425 (Electronic)
IS  - 2076-3425 (Linking)
VI  - 12
IP  - 7
DP  - 2022 Jul 20
TI  - PS-NPs Induced Neurotoxic Effects in SHSY-5Y Cells via Autophagy Activation and 
      Mitochondrial Dysfunction.
LID - 10.3390/brainsci12070952 [doi]
LID - 952
AB  - Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely 
      detected in the environment and organisms, posing potential threats to both 
      ecosystems and human health. PS-NPs have been proven to penetrate the blood-brain 
      barrier and increase the incidence of neurodegenerative diseases. However, 
      information relating to the pathogenic molecular mechanism is still unclear. This 
      study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human 
      neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious 
      mitochondrial damages, as evidenced by inhibited cell proliferation, increased 
      lactate dehydrogenase release, stimulated oxidative stress responses, elevated 
      Ca(2+) level and apoptosis, and reduced mitochondrial membrane potential and 
      adenosine triphosphate levels. The increased release of cytochrome c and the 
      overexpression of apoptosis-related proteins apoptotic protease activating 
      factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and 
      caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In 
      addition, the upregulation of autophagy markers light chain 3-II (LC3-II), 
      Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could 
      promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the 
      regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration 
      of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity 
      and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could 
      induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria 
      dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial 
      damages caused by oxidative stress could potentially be involved in the 
      pathological mechanisms for PS-NP-induced neurodegenerative diseases.
FAU - Tang, Qisheng
AU  - Tang Q
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Li, Tianwen
AU  - Li T
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Chen, Kezhu
AU  - Chen K
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Deng, Xiangyang
AU  - Deng X
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Zhang, Quan
AU  - Zhang Q
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Tang, Hailiang
AU  - Tang H
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Shi, Zhifeng
AU  - Shi Z
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Zhu, Tongming
AU  - Zhu T
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
FAU - Zhu, Jianhong
AU  - Zhu J
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, National Center for Neurological Disorders, National Key Laboratory 
      for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of 
      Brain Function and Regeneration, MOE Frontiers Center for Brain Science, 12 
      Wulumuqi Zhong Rd., Shanghai 200040, China.
LA  - eng
PT  - Journal Article
DEP - 20220720
PL  - Switzerland
TA  - Brain Sci
JT  - Brain sciences
JID - 101598646
PMC - PMC9321807
OTO - NOTNLM
OT  - autophagy
OT  - mitochondrial oxidative stress
OT  - neurotoxicity
OT  - polystyrene nanoparticles
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/20
CRDT- 2022/07/27 01:11
PHST- 2022/06/09 00:00 [received]
PHST- 2022/07/09 00:00 [revised]
PHST- 2022/07/18 00:00 [accepted]
PHST- 2022/07/27 01:11 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/20 00:00 [pmc-release]
AID - brainsci12070952 [pii]
AID - brainsci-12-00952 [pii]
AID - 10.3390/brainsci12070952 [doi]
PST - epublish
SO  - Brain Sci. 2022 Jul 20;12(7):952. doi: 10.3390/brainsci12070952.