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Polyhexamethyleneguanidine phosphate‐induced cytotoxicity is mediated by endoplasmic reticulum stress
Author(s) -
Jung Young-Suk,
Kim Sou Hyun,
Lee Seunghyun,
Son Seung Won
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03883
Subject(s) - cytotoxicity , apoptosis , unfolded protein response , endoplasmic reticulum , toxicity , chemistry , viability assay , microbiology and biotechnology , programmed cell death , pharmacology , in vitro , biochemistry , biology , organic chemistry
Polyhexamethyleneguanidine phosphate (PHMG‐P) is a widely used polymeric antimicrobial agent to induce significant pulmonary toxicity. Several studies have reported that the liver also can be a target organ of PHMG toxicity, but the exact effect of this compound on liver cells is not well understood. To identify the mechanism of PHMG hepatotoxicity, HepG2 cells were exposed to PHMG‐P for 72 h. Cell viability was significantly decreased by PHMG‐P in a time‐and concentration‐dependent manner. Mitochondrial membrane potential was markedly reduced by PHMG‐P and the apoptotic signaling cascade was activated. The increases observed in CHOP, p‐IRE, and p‐JNK levels in PHMG‐P‐treated cells indicated the induction of ER stress. To verify the role of ER stress in PHMG‐P‐induced cytotoxicity, HepG2 cells were pretreated with the chemical chaperone, TUDCA and then co‐treated with TUDCA and PHMG‐P for 24 h. Interestingly, TUDCA inhibited PHMG‐P‐induced ER stress and cytotoxicity in a dose‐dependent manner. Apoptotic cell death and mitochondrial depolarization were also prevented by TUDCA. Proteins involved in the apoptotic pathway were all normalized to their control levels in TUDCA‐treated cells. In conclusion, the results suggest that PHMG‐P induced significant cytotoxicity in liver cells and ER stress‐mediated apoptosis may be an important mechanism mediating this hepatotoxicity. Support or Funding Information This study was funded by Nano‐Material Technology Development Program through the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (NRF‐2018M3A7B4071233).