PMID- 25872712
OWN - NLM
STAT- MEDLINE
DCOM- 20150915
LR  - 20151119
IS  - 1001-0742 (Print)
IS  - 1001-0742 (Linking)
VI  - 30
DP  - 2015 Apr 1
TI  - Sodium fluoride induces apoptosis through reactive oxygen species-mediated 
      endoplasmic reticulum stress pathway in Sertoli cells.
PG  - 81-9
LID - S1001-0742(15)00056-X [pii]
LID - 10.1016/j.jes.2014.11.004 [doi]
AB  - Excessive fluoride exposure is known to contribute to reproductive system 
      dysfunction, ultimately leading to pathological damage and apoptosis in cells. 
      Although both oxidative and endoplasmic reticulum (ER) stresses have been 
      implicated in fluorosis, the signaling pathways and their roles in sodium 
      fluoride (NaF)-induced apoptosis of Sertoli cells have been sparsely described. 
      In this study, oxidative damage, ER stress, and apoptosis were analyzed after 
      Sertoli cells were treated with varying doses of NaF for 24hr. Moreover, the 
      antioxidant N-acetylcysteine (NAC) and pro-apoptotic transcription factor CHOP 
      knockdown were used to clarify the precise interplay between reactive oxygen 
      species (ROS), ER stress and their roles in NaF-induced apoptosis in Sertoli 
      cells. The present study indicated that NaF significantly decreased cell 
      viability and induced apoptosis in Sertoli cells. In addition, NaF exposure 
      facilitated the accumulation of ROS and increased nuclear translocation of 
      nuclear factor erythroid 2-related factor 2 (Nrf2) in Sertoli cells. Treatment 
      with NAC caused remarkable recovery from these NaF-induced responses. Meanwhile, 
      excessive NaF triggered ER stress as evidenced by up-regulated glucose-regulated 
      protein 78 kDa (GRP78), PKR-like ER kinase (PERK), phosphorylation of eukaryotic 
      translation initiation factor 2alpha (p-eIF2alpha) and CCAAT/enhancer-binding 
      protein-homologous protein (CHOP), without affecting total eukaryotic translation 
      initiation factor 2alpha (eIF2alpha). NAC effectively blocked the activation of ER 
      stress, suggesting that NaF-induced ROS is an early event that triggers ER 
      stress. Taken together, the results demonstrate that the ROS-mediated ER stress 
      pathway is the crucial mechanistic event involved in NaF-induced apoptosis of 
      Sertoli cells.
CI  - Copyright (c) 2015. Published by Elsevier B.V.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Environmental Health, College of Public Health, Zhengzhou 
      University, Zhengzhou 450001, China. Electronic address: xuballyy@163.com.
FAU - Lin, Xinwei
AU  - Lin X
AD  - Department of Nephrology, 152 Hospital of PLA, Pingdingshan 467000, China.
FAU - Huang, Hui
AU  - Huang H
AD  - Department of Environmental Health, College of Public Health, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Feng, Demin
AU  - Feng D
AD  - Department of Environmental Health, College of Public Health, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Ba, Yue
AU  - Ba Y
AD  - Department of Environmental Health, College of Public Health, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Cheng, Xuemin
AU  - Cheng X
AD  - Department of Environmental Health, College of Public Health, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Cui, Liuxin
AU  - Cui L
AD  - Department of Environmental Health, College of Public Health, Zhengzhou 
      University, Zhengzhou 450001, China. Electronic address: xuballyy@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150224
PL  - Netherlands
TA  - J Environ Sci (China)
JT  - Journal of environmental sciences (China)
JID - 100967627
RN  - 0 (Biomarkers)
RN  - 0 (Ddit3 protein, rat)
RN  - 0 (Reactive Oxygen Species)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 8ZYQ1474W7 (Sodium Fluoride)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/metabolism
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Biomarkers/metabolism
MH  - Dose-Response Relationship, Drug
MH  - *Endoplasmic Reticulum Stress
MH  - Gene Knockdown Techniques
MH  - Male
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - *Reactive Oxygen Species
MH  - Sertoli Cells
MH  - Sodium Fluoride/*toxicity
MH  - Testis
MH  - Transcription Factor CHOP/genetics/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Endoplasmic reticulum stress
OT  - Reactive oxygen species
OT  - Sertoli cell
OT  - Sodium fluoride
EDAT- 2015/04/16 06:00
MHDA- 2015/09/16 06:00
CRDT- 2015/04/16 06:00
PHST- 2014/10/22 00:00 [received]
PHST- 2014/10/28 00:00 [revised]
PHST- 2014/11/11 00:00 [accepted]
PHST- 2015/04/16 06:00 [entrez]
PHST- 2015/04/16 06:00 [pubmed]
PHST- 2015/09/16 06:00 [medline]
AID - S1001-0742(15)00056-X [pii]
AID - 10.1016/j.jes.2014.11.004 [doi]
PST - ppublish
SO  - J Environ Sci (China). 2015 Apr 1;30:81-9. doi: 10.1016/j.jes.2014.11.004. Epub 
      2015 Feb 24.