Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway

Du, Zhong-jun, Cui, Guan-qun, Zhang, Juan, Liu, Xiao-mei, Zhang, Zhi-hu, Jia, Qiang, Ng, Jack C., Peng, Cheng, Bo, Cun-xiang and Shao, Hua (2017) Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway. International Journal of Nanomedicine, 12 2179-2188. doi:10.2147/IJN.S127904


Author Du, Zhong-jun
Cui, Guan-qun
Zhang, Juan
Liu, Xiao-mei
Zhang, Zhi-hu
Jia, Qiang
Ng, Jack C.
Peng, Cheng
Bo, Cun-xiang
Shao, Hua
Title Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway
Journal name International Journal of Nanomedicine   Check publisher's open access policy
ISSN 1178-2013
1176-9114
Publication date 2017-01-01
Sub-type Article (original research)
DOI 10.2147/IJN.S127904
Open Access Status DOI
Volume 12
Start page 2179
End page 2188
Total pages 10
Place of publication Macclesfield, United Kingdom
Publisher Dove Medical Press
Collection year 2018
Language eng
Abstract 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.
Keyword Silica nanoparticles
Cardiotoxicity
Connexin 43
Cell death
Gap junction
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
National Research Centre for Environmental Toxicology Publications
 
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