PMID- 36346508
OWN - NLM
STAT- MEDLINE
DCOM- 20230815
LR  - 20231029
IS  - 1573-6822 (Electronic)
IS  - 0742-2091 (Print)
IS  - 0742-2091 (Linking)
VI  - 39
IP  - 4
DP  - 2023 Aug
TI  - Silica nanoparticles induce ovarian granulosa cell apoptosis via activation of 
      the PERK-ATF4-CHOP-ERO1alpha pathway-mediated IP3R1-dependent calcium mobilization.
PG  - 1715-1734
LID - 10.1007/s10565-022-09776-4 [doi]
AB  - Ambient particulate matters (PMs) have adverse effects in human and animal female 
      reproductive health. Silica nanoparticles (SNPs), as a major component of PMs, 
      can induce follicular atresia via the promotion of ovarian granulosa cell 
      apoptosis. However, the molecular mechanisms of apoptosis induced by SNPs are not 
      very clear. This work focuses on revealing the mechanisms of ER stress on 
      SNP-induced apoptosis. Our results showed that spherical Stober SNPs (110 nm, 
      25.0 mg/kg b.w.) induced follicular atresia via the promotion of granulosa cell 
      apoptosis by intratracheal instillation in vivo; meanwhile, SNPs decreased the 
      viability and increase apoptosis in granulosa cells in vitro. SNPs were taken up 
      and accumulated in the vesicles of granulosa cells. Additionally, our results 
      found that SNPs increased calcium ion (Ca(2+)) concentration in granulosa cell 
      cytoplasm. Furthermore, SNPs activated ER stress via an increase in the PERK and 
      ATF6 pathway-related protein levels and IP3R1-dependent calcium mobilization via 
      an increase in IP3R1 level. In addition, 4-PBA restored IP3R1-dependent calcium 
      mobilization and decreased apoptosis via the inhibition of ER stress. The 
      ATF4-C/EBP homologous protein (CHOP)-ER oxidoreductase 1 alpha (ERO1alpha) pathway 
      regulated SNP-induced IP3R1-dependent calcium mobilization and cell apoptosis via 
      ATF4, CHOP, and ERO1alpha depletion in ovarian granulosa cells. Herein, we 
      demonstrate that ER stress cooperated in SNP-induced ovarian toxicity via 
      activation of IP3R1-mediated calcium mobilization, leading to apoptosis, in which 
      the PERK-ATF4-CHOP-ERO1alpha pathway plays an essential role in ovarian granulosa 
      cells.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Nature B.V.
FAU - Chen, Fenglei
AU  - Chen F
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      People's Republic of China. flchen@yzu.edu.cn.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of 
      China. flchen@yzu.edu.cn.
AD  - Joint International Research Laboratory of Agriculture and Agri-Product Safety of 
      the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, 
      Jiangsu, People's Republic of China. flchen@yzu.edu.cn.
FAU - Sun, Jiarong
AU  - Sun J
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      People's Republic of China.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of 
      China.
FAU - Wang, Yujing
AU  - Wang Y
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      People's Republic of China.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of 
      China.
FAU - Grunberger, Jason William
AU  - Grunberger JW
AD  - Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 
      Salt Lake City, UT, USA.
AD  - Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT, USA.
FAU - Zheng, Zhen
AU  - Zheng Z
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      People's Republic of China.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of 
      China.
FAU - Khurana, Nitish
AU  - Khurana N
AD  - Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 
      Salt Lake City, UT, USA.
AD  - Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT, USA.
FAU - Xu, Xianyu
AU  - Xu X
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      People's Republic of China.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of 
      China.
FAU - Zhou, Xin
AU  - Zhou X
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      People's Republic of China.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of 
      China.
AD  - Joint International Research Laboratory of Agriculture and Agri-Product Safety of 
      the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, 
      Jiangsu, People's Republic of China.
FAU - Ghandehari, Hamidreza
AU  - Ghandehari H
AD  - Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 
      Salt Lake City, UT, USA.
AD  - Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT, USA.
AD  - Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, 
      USA.
FAU - Zhang, Jinlong
AU  - Zhang J
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      People's Republic of China. zjl@yzu.edu.cn.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of 
      China. zjl@yzu.edu.cn.
AD  - Joint International Research Laboratory of Agriculture and Agri-Product Safety of 
      the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, 
      Jiangsu, People's Republic of China. zjl@yzu.edu.cn.
LA  - eng
GR  - R01 ES024681/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221108
PL  - Switzerland
TA  - Cell Biol Toxicol
JT  - Cell biology and toxicology
JID - 8506639
RN  - SY7Q814VUP (Calcium)
RN  - EC 1.- (Oxidoreductases)
RN  - 7631-86-9 (Silicon Dioxide)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - 0 (ATF4 protein, human)
RN  - 145891-90-3 (Activating Transcription Factor 4)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - *Calcium/metabolism
MH  - Oxidoreductases/metabolism
MH  - Silicon Dioxide/toxicity
MH  - Follicular Atresia
MH  - Apoptosis
MH  - Granulosa Cells/metabolism
MH  - *Nanoparticles
MH  - Endoplasmic Reticulum Stress
MH  - eIF-2 Kinase/metabolism
MH  - Activating Transcription Factor 4/metabolism
PMC - PMC10604358
MID - NIHMS1937461
OTO - NOTNLM
OT  - Apoptosis
OT  - Calcium mobilization
OT  - ER stress
OT  - Follicular atresia
OT  - Ovarian granulosa cells
OT  - Silica nanoparticles
COIS- Conflict of interest The authors declare no competing interests.
EDAT- 2022/11/09 06:00
MHDA- 2023/08/15 06:42
PMCR- 2024/08/01
CRDT- 2022/11/08 11:16
PHST- 2022/07/27 00:00 [received]
PHST- 2022/10/06 00:00 [accepted]
PHST- 2024/08/01 00:00 [pmc-release]
PHST- 2023/08/15 06:42 [medline]
PHST- 2022/11/09 06:00 [pubmed]
PHST- 2022/11/08 11:16 [entrez]
AID - 10.1007/s10565-022-09776-4 [pii]
AID - 10.1007/s10565-022-09776-4 [doi]
PST - ppublish
SO  - Cell Biol Toxicol. 2023 Aug;39(4):1715-1734. doi: 10.1007/s10565-022-09776-4. 
      Epub 2022 Nov 8.