PMID- 31558022
OWN - NLM
STAT- MEDLINE
DCOM- 20200727
LR  - 20200930
IS  - 1530-6992 (Electronic)
IS  - 1530-6984 (Linking)
VI  - 19
IP  - 11
DP  - 2019 Nov 13
TI  - Polystyrene Nanoparticles Reduced ROS and Inhibited Ferroptosis by Triggering 
      Lysosome Stress and TFEB Nucleus Translocation in a Size-Dependent Manner.
PG  - 7781-7792
LID - 10.1021/acs.nanolett.9b02795 [doi]
AB  - Though plastic nanoparticles have already raised much concern for their potential 
      impact on health, our understanding of their biological effects is still utterly 
      limited. Here we demonstrate for the first time that carboxyl-modified 
      polystyrene nanoparticles (CPS) could effectively inhibit ferroptosis as a result 
      of reduced cellular ROS which was triggered by transcription factor EB (TFEB) 
      nucleus translocation. In this process, CPS first entered cells via 
      macropinocytosis, then CPS-containing macropinosomes fused with lysosomes and 
      expanded into abnormal lysosome-like large vacuoles in vacuolar-type H(+)-ATPase 
      (V-ATPase) and aquaporins (AQPs) in a dependent way. These large vacuoles were 
      detected both in vitro and in vivo, which was found to be a sign of lysosome 
      stress. The lysosome stress induced deactivation of mammalian target of rapamycin 
      (mTOR) which led to nucleus translocation of TFEB. Then, TFEB-dependent enhanced 
      expression of lysosomal proteins and superoxide dismutase (SOD) which ultimately 
      led to ROS reduction and inhibition of ferroptosis. Knockout of TFEB-enhanced 
      ferroptosis was triggered by Erastin and abolished the effect of CPS on ROS and 
      ferroptosis. In summary, our results reveal a novel mechanism whereby CPS reduced 
      ROS and inhibited ferroptosis in a TFEB-dependent way. These findings have 
      important implications for understanding the biological effects of polystyrene 
      nanoparticles and searching for new anti-ROS and antiferroptosis particles or 
      reagents.
FAU - Li, Lin
AU  - Li L
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, College of Polymer Science and 
      Engineering , Sichuan University , Chengdu 610065 , China.
FAU - Sun, Shili
AU  - Sun S
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, College of Polymer Science and 
      Engineering , Sichuan University , Chengdu 610065 , China.
FAU - Tan, Lingli
AU  - Tan L
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, College of Polymer Science and 
      Engineering , Sichuan University , Chengdu 610065 , China.
FAU - Wang, Yuanfang
AU  - Wang Y
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, College of Polymer Science and 
      Engineering , Sichuan University , Chengdu 610065 , China.
FAU - Wang, Luyao
AU  - Wang L
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, College of Polymer Science and 
      Engineering , Sichuan University , Chengdu 610065 , China.
FAU - Zhang, Zhirong
AU  - Zhang Z
AUID- ORCID: 0000-0001-9118-5394
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, College of Polymer Science and 
      Engineering , Sichuan University , Chengdu 610065 , China.
FAU - Zhang, Ling
AU  - Zhang L
AUID- ORCID: 0000-0003-3237-4544
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, College of Polymer Science and 
      Engineering , Sichuan University , Chengdu 610065 , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191002
PL  - United States
TA  - Nano Lett
JT  - Nano letters
JID - 101088070
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Polystyrenes)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TFEB protein, human)
SB  - IM
EIN - Nano Lett. 2019 Dec 11;19(12):9170. PMID: 31755724
MH  - Animals
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*metabolism
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Ferroptosis/*drug effects
MH  - Humans
MH  - Lysosomes/*drug effects/metabolism
MH  - Mice
MH  - *Nanoparticles/chemistry
MH  - Pinocytosis/drug effects
MH  - Polystyrenes/chemistry/*pharmacology
MH  - Protein Transport/drug effects
MH  - RAW 264.7 Cells
MH  - Reactive Oxygen Species/*metabolism
OTO - NOTNLM
OT  - Carboxyl polystyrene nanoparticles
OT  - ROS
OT  - TFEB
OT  - ferroptosis
OT  - size-dependent way
OT  - vacuole
EDAT- 2019/09/29 06:00
MHDA- 2020/07/28 06:00
CRDT- 2019/09/28 06:00
PHST- 2019/09/29 06:00 [pubmed]
PHST- 2020/07/28 06:00 [medline]
PHST- 2019/09/28 06:00 [entrez]
AID - 10.1021/acs.nanolett.9b02795 [doi]
PST - ppublish
SO  - Nano Lett. 2019 Nov 13;19(11):7781-7792. doi: 10.1021/acs.nanolett.9b02795. Epub 
      2019 Oct 2.