Open AccessArachidonic acid suppresses hepatic cell growth through ROS ‐mediated activation of transglutaminase
Author(s) -
Qin XianYang,
Lu Jun,
Cai Muyi,
Kojima Soichi
Publication year - 2018
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12511
Subject(s) - reactive oxygen species , tissue transglutaminase , arachidonic acid , oxidative stress , cell growth , carcinogenesis , inflammation , chemistry , microbiology and biotechnology , small hairpin rna , biochemistry , cancer research , enzyme , biology , apoptosis , immunology , gene knockdown , gene
We previously reported a profound augmentation in the hepatic levels of a pro‐inflammatory precursor, arachidonic acid ( AA ), during liver tumorigenesis. Here, we report a critical role of the induced reactive oxygen species ( ROS )‐mediated cellular activation of a protein cross‐linking enzyme, transglutaminase 2 ( TG 2), in liver injury by AA . In cultures of hepatic cells, AA dose‐dependently suppressed cell growth, which accompanied the induced nuclear accumulation of TG 2, as demonstrated in EGFP ‐tagged, TG 2‐overexpressing hepatic cells. A chemical inhibitor/sh RNA that acts against TG 2 prevented AA ‐mediated cell growth suppression. In addition, AA provoked significant production of ROS , and antioxidants blocked AA ‐induced activation of nuclear TG 2 and hepatic cell growth suppression. We propose that AA ‐mediated oxidative stress and TG 2 transamidase activity might contribute to chronic liver injury and inflammation and thereby serve as potential therapeutic targets for the chemoprevention of hepatocellular carcinoma.