PMID- 28356735
OWN - NLM
STAT- MEDLINE
DCOM- 20170522
LR  - 20220330
IS  - 1178-2013 (Electronic)
IS  - 1176-9114 (Print)
IS  - 1176-9114 (Linking)
VI  - 12
DP  - 2017
TI  - Inhibition of gap junction intercellular communication is involved in silica 
      nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial 
      pathway.
PG  - 2179-2188
LID - 10.2147/IJN.S127904 [doi]
AB  - Gap junction intercellular communication (GJIC) between cardiomyocytes is 
      essential for synchronous heart contraction and relies on connexin-containing 
      channels. Connexin 43 (Cx43) is a major component involved in GJIC in heart 
      tissue, and its abnormal expression is closely associated with various cardiac 
      diseases. Silica nanoparticles (SNPs) are known to induce cardiovascular 
      toxicity. However, the mechanisms through which GJIC plays a role in 
      cardiomyocytes apoptosis induced by SNPs remain unknown. The aim of the present 
      study is to determine whether SNPs-decreased GJIC promotes apoptosis in rat 
      cardiomyocytes cell line (H9c2 cells) via the mitochondrial pathway using CCK-8 
      Kit, scrape-loading dye transfer technique, Annexin V/PI double-staining assays, 
      and Western blot analysis. The results showed that SNPs elicited cytotoxicity in 
      H9c2 cells in a time- and concentration-dependent manner. SNPs also reduced GJIC 
      in H9c2 cells in a concentration-dependent manner through downregulation of Cx43 
      and upregulation of P-Cx43. Inhibition of gap junctions by gap junction blocker 
      carbenoxolone disodium resulted in decreased survival and increased apoptosis, 
      whereas enhancement of the gap junctions by retinoic acid led to enhanced 
      survival but decreased apoptosis. Furthermore, SNPs-induced apoptosis through the 
      disrupted functional gap junction was correlated with abnormal expressions of the 
      proteins involved in the mitochondrial pathway-related apoptosis such as 
      Bcl-2/Bax, cytochrome C, Caspase-9, and Caspase-3. Taken together, our results 
      provide the first evidence that SNPs-decreased GJIC promotes apoptosis in 
      cardiomyocytes via the mitochondrial pathway. In addition, downregulation of GJIC 
      by SNPs in cardiomyocytes is mediated through downregulation of Cx43 and 
      upregulation of P-Cx43. These results suggest that in rat cardiomyocytes cell 
      line, GJIC plays a protective role in SNPs-induced apoptosis and that GJIC may be 
      one of the targets for SNPs-induced biological effects.
FAU - Du, Zhong-Jun
AU  - Du ZJ
AD  - Department of Toxicology, Shandong Academy of Occupational Health and 
      Occupational Medicine, Shandong Academy of Medical Sciences.
FAU - Cui, Guan-Qun
AU  - Cui GQ
AD  - Department of Respiratory Medicine, Qilu Children's Hospital of Shandong 
      University, Jinan.
FAU - Zhang, Juan
AU  - Zhang J
AD  - Department of Toxicology, Shandong Academy of Occupational Health and 
      Occupational Medicine, Shandong Academy of Medical Sciences.
FAU - Liu, Xiao-Mei
AU  - Liu XM
AD  - Department of Radiation Chemistry and Toxicology, School of Public Health, Jilin 
      University, Changchun, People's Republic of China.
FAU - Zhang, Zhi-Hu
AU  - Zhang ZH
AD  - Department of Toxicology, Shandong Academy of Occupational Health and 
      Occupational Medicine, Shandong Academy of Medical Sciences.
FAU - Jia, Qiang
AU  - Jia Q
AD  - Department of Toxicology, Shandong Academy of Occupational Health and 
      Occupational Medicine, Shandong Academy of Medical Sciences.
FAU - Ng, Jack C
AU  - Ng JC
AD  - National Research Centre for Environmental Toxicology-Entox, The University of 
      Queensland, Brisbane, QLD, Australia.
FAU - Peng, Cheng
AU  - Peng C
AD  - Department of Toxicology, Shandong Academy of Occupational Health and 
      Occupational Medicine, Shandong Academy of Medical Sciences; National Research 
      Centre for Environmental Toxicology-Entox, The University of Queensland, 
      Brisbane, QLD, Australia.
FAU - Bo, Cun-Xiang
AU  - Bo CX
AD  - Department of Toxicology, Shandong Academy of Occupational Health and 
      Occupational Medicine, Shandong Academy of Medical Sciences.
FAU - Shao, Hua
AU  - Shao H
AD  - Department of Toxicology, Shandong Academy of Occupational Health and 
      Occupational Medicine, Shandong Academy of Medical Sciences.
LA  - eng
PT  - Journal Article
DEP - 20170320
PL  - New Zealand
TA  - Int J Nanomedicine
JT  - International journal of nanomedicine
JID - 101263847
RN  - 5688UTC01R (Tretinoin)
RN  - 7631-86-9 (Silicon Dioxide)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - *Cell Communication/drug effects
MH  - Cell Line
MH  - Gap Junctions/drug effects/*metabolism
MH  - Mitochondria/*metabolism
MH  - Myocytes, Cardiac/*cytology/metabolism
MH  - Nanoparticles/*chemistry/ultrastructure
MH  - Rats
MH  - Signal Transduction/*drug effects
MH  - Silicon Dioxide/*pharmacology
MH  - Time Factors
MH  - Tretinoin/pharmacology
PMC - PMC5367603
OTO - NOTNLM
OT  - cardiotoxicity
OT  - cell death
OT  - connexin 43
OT  - gap junction
OT  - silica nanoparticles
COIS- Disclosure The authors declare that there is no conflict of interest in this 
      work.
EDAT- 2017/03/31 06:00
MHDA- 2017/05/23 06:00
PMCR- 2017/03/20
CRDT- 2017/03/31 06:00
PHST- 2017/03/31 06:00 [entrez]
PHST- 2017/03/31 06:00 [pubmed]
PHST- 2017/05/23 06:00 [medline]
PHST- 2017/03/20 00:00 [pmc-release]
AID - ijn-12-2179 [pii]
AID - 10.2147/IJN.S127904 [doi]
PST - epublish
SO  - Int J Nanomedicine. 2017 Mar 20;12:2179-2188. doi: 10.2147/IJN.S127904. 
      eCollection 2017.