Arachidonic acid suppresses hepatic cell growth through ROS-mediated activation of transglutaminase.

Abstract:

: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 (TG2), in liver injury by AA. In cultures of hepatic cells, AA dose-dependently suppressed cell growth, which accompanied the induced nuclear accumulation of TG2, as demonstrated in EGFP-tagged, TG2-overexpressing hepatic cells. A chemical inhibitor/shRNA that acts against TG2 prevented AA-mediated cell growth suppression. In addition, AA provoked significant production of ROS, and antioxidants blocked AA-induced activation of nuclear TG2 and hepatic cell growth suppression. We propose that AA-mediated oxidative stress and TG2 transamidase activity might contribute to chronic liver injury and inflammation and thereby serve as potential therapeutic targets for the chemoprevention of hepatocellular carcinoma.

journal_name

FEBS Open Bio

journal_title

FEBS open bio

authors

Qin XY,Lu J,Cai M,Kojima S

doi

10.1002/2211-5463.12511

subject

Has Abstract

pub_date

2018-09-11 00:00:00

pages

1703-1710

issue

10

issn

2211-5463

pii

FEB412511

journal_volume

8

pub_type

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