PMID- 33652285
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20210513
IS  - 1879-1298 (Electronic)
IS  - 0045-6535 (Linking)
VI  - 275
DP  - 2021 Jul
TI  - Polybrominated diphenyl ethers quinone-induced intracellular protein oxidative 
      damage triggers ubiquitin-proteasome and autophagy-lysosomal system activation in 
      LO2 cells.
PG  - 130034
LID - S0045-6535(21)00503-8 [pii]
LID - 10.1016/j.chemosphere.2021.130034 [doi]
AB  - Polybrominated diphenyl ethers (PBDEs), a kind of flame retardants, were widely 
      used in the furniture, textile and electronics industries. Because of their 
      lipophilic, persistent and bio-accumulative properties, PBDEs were listed on the 
      Stockholm Convention as typical persistent organic pollutants (POPs). We have 
      previously reported that a highly active, quinone-type metabolite of PBDEs 
      (PBDEQ) causes DNA damage and subsequently triggers apoptosis. However, it is 
      remaining unclear whether PBDEQ provokes protein damage and stimulates 
      corresponding signaling cascade. Using human normal liver (LO2) cells as an 
      in vitro model, we demonstrated that PBDEQ causes oxidative protein damage 
      through excess reactive oxygen species (ROS). Consistently, we found PBDEQ 
      exposure causes the depletion of protein thiol group, the appearance of carbonyl 
      group and the accumulation of protein aggregates. Endoplasmic reticulum (ER) 
      stress was involved in the repair of oxidized proteins. Under the scenario of 
      severe damage, LO2 cells degrade oxidized proteins through ubiquitin-proteasome 
      system (UPS) and autophagy. The blockage of these protein degradation pathways 
      aggravates PBDEQ-induced cytotoxicity in LO2 cells, whilst antioxidant 
      N-acetyl-cysteine (NAC) rescues PBDEQ-induced oxidative protein damage 
      conversely. In summary, our current study first demonstrated PBDEQ-induced 
      protein oxidative damage in LO2 cells, which offer a better understanding of the 
      cytotoxicity of PBDEs and corresponding metabolites.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Wang, Yuting
AU  - Wang Y
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Xu, Lei
AU  - Xu L
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Peng, Lu
AU  - Peng L
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Fang, Changyu
AU  - Fang C
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Qin, Qi
AU  - Qin Q
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Lv, Xuying
AU  - Lv X
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Liu, Zixuan
AU  - Liu Z
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Yang, Bingwei
AU  - Yang B
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Song, Erqun
AU  - Song E
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China.
FAU - Song, Yang
AU  - Song Y
AD  - Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      400715, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, 
      Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 
      Beijing, 100085, China. Electronic address: ysong@swu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210223
PL  - England
TA  - Chemosphere
JT  - Chemosphere
JID - 0320657
RN  - 0 (Flame Retardants)
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 0 (Quinones)
RN  - 0 (Ubiquitin)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Autophagy
MH  - *Flame Retardants/toxicity
MH  - *Halogenated Diphenyl Ethers/toxicity
MH  - Humans
MH  - Lysosomes
MH  - Oxidative Stress
MH  - Proteasome Endopeptidase Complex
MH  - Quinones
MH  - Ubiquitin
OTO - NOTNLM
OT  - Autophagy
OT  - Endoplasmic reticulum stress
OT  - PBDEQ
OT  - Protein oxidative damage
OT  - Ubiquitin-proteasome system
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/03/03 06:00
MHDA- 2021/05/14 06:00
CRDT- 2021/03/02 20:12
PHST- 2020/12/13 00:00 [received]
PHST- 2021/02/03 00:00 [revised]
PHST- 2021/02/15 00:00 [accepted]
PHST- 2021/03/03 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
PHST- 2021/03/02 20:12 [entrez]
AID - S0045-6535(21)00503-8 [pii]
AID - 10.1016/j.chemosphere.2021.130034 [doi]
PST - ppublish
SO  - Chemosphere. 2021 Jul;275:130034. doi: 10.1016/j.chemosphere.2021.130034. Epub 
      2021 Feb 23.