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Tang N, Cai Z, Chen H, et al. Involvement of gap junctions in propylthiouracil-induced cytotoxicity in BRL-3A cells. Exp Ther Med. 2019;17(4):2799-2806doi: 10.3892/etm.2019.7244.
Tang, N., Cai, Z., Chen, H., Cao, L., Chen, B., & Lin, B. (2019). Involvement of gap junctions in propylthiouracil-induced cytotoxicity in BRL-3A cells. Experimental and therapeutic medicine, 17(4), 2799-2806. https://doi.org/10.3892/etm.2019.7244
Tang, Nan, et al. "Involvement of gap junctions in propylthiouracil-induced cytotoxicity in BRL-3A cells." Experimental and therapeutic medicine vol. 17,4 (2019): 2799-2806. doi: https://doi.org/10.3892/etm.2019.7244
Tang N, Cai Z, Chen H, Cao L, Chen B, Lin B. Involvement of gap junctions in propylthiouracil-induced cytotoxicity in BRL-3A cells. Exp Ther Med. 2019 Apr;17(4):2799-2806. doi: 10.3892/etm.2019.7244. Epub 2019 Feb 06. PMID: 30906468; PMCID: PMC6425232.
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Exp Ther Med. 2019 Apr;17(4):2799-2806. doi: 10.3892/etm.2019.7244. Epub 2019 Feb 06.

Involvement of gap junctions in propylthiouracil-induced cytotoxicity in BRL-3A cells.

Experimental and therapeutic medicine

Nan Tang, Ziqing Cai, Hongpeng Chen, Longbin Cao, Bo Chen, Bihua Lin

Affiliations

  1. School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
  2. School of Information Engineering, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
  3. School of Basic Medical Sciences, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.

PMID: 30906468 PMCID: PMC6425232 DOI: 10.3892/etm.2019.7244

Abstract

Gap junctions (GJs), which are important plasma membrane channels for the transfer of signaling molecules between adjacent cells, have been implicated in drug-induced liver injury. However, the influence and the underlying mechanisms of GJs in propylthiouracil (PTU)-induced hepatotoxicity are unclear. In the present study, distinct manipulations were performed to regulate GJ function in the BRL-3A rat liver cell line. The results indicated that the toxic effect of PTU in BRL-3A cells was mediated by GJ intercellular communication, as cell death was significantly attenuated in the absence of functional GJ channels. Furthermore, the specific knockdown of connexin-32 (Cx32; a major GJ component protein in hepatocytes) using small interfering RNA was observed to decrease necrosis, intracellular PTU content and the level of reactive oxygen species (ROS) following PTU exposure. These observations demonstrated that suppressing GJ Cx32 could confer protection against PTU-induced cytotoxicity through decreasing the accumulation of PTU and ROS. To the best of our knowledge, the present study is the first to demonstrate the role and possible underlying mechanisms of GJs in the regulation of PTU-induced toxicity in BRL-3A rat liver cells.

Keywords: BRL-3A; cytotoxicity; gap junction; mechanism; propylthiouracil

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