Arachidonic acid suppresses hepatic cell growth through ROS‐mediated activation of transglutaminase. Issue 10 (11th September 2018)

• Record Type: Journal Article
• Authors: Qin, Xian‐Yang; Lu, Jun; Cai, Muyi; Kojima, Soichi
• Is Part Of: FEBS open bio. Volume 8:Issue 10(2018)
• Page Start: 1703
• Page End: 1710
• Publication Date: 2018-09-11
• Subjects: arachidonic acid -- corn peptides -- hepatic cell injury -- nuclear transglutaminase 2 -- reactive oxygen species; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12511
• Languages: English
• ISSNs: 2211-5463

Abstract

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. Abstract : The hepatic levels of a pro‐inflammatory precursor, arachidonic acid (AA), are increased during liver tumorigenesis. Here, we report a role of reactive oxygen species‐mediated cellular activation of a protein cross‐linking enzyme, transglutaminase 2 (TG2), in liver injury by AA. We propose that AA‐mediated oxidative stress and TG2 transamidase activity might serve as therapeutic targets for the chemoprevention of hepatocellular carcinoma.