Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Reactive oxygen species (ROS) can react with highly unsaturated fatty acids (HUFAs) of membrane phospholipids to induce lipid peroxidation. Thus, HUFA-containing phospholipids levels might be correlated with sensitivity to ROS-induced cell death. Acyl-CoA synthetase long-chain family members (ACSLs) catalyze the synthesis of long-chain acyl-CoA from long-chain fatty acids. Among five ACSL isozymes, ACSL4 prefers HUFAs as its substrate and thus plays an important role in maintaining HUFA-containing phospholipids levels. We recently reported that the levels of HUFA-containing phospholipids decreased in lungs from ACSL4-deficient (KO) mice and that ACSL4 deficiency attenuated both paraquat- and methotrexate-induced lung injury via the suppression of lipid peroxidation. In this study, we investigated the role of ACSL4 in bleomycin-induced pulmonary fibrosis. We revealed that after administration of bleomycin, the level of phosphatidylcholine (16:0/20:4)-derived peroxide was increased in wild type (WT) mice, the increase was significantly suppressed in KO mice. Similarly, the levels of fibrosis markers such as hydroxyproline and α-SMA, and the gene expression of E-cadherin and IGF-1 were increased in WT mice, but these increases were suppressed in KO mice. Furthermore, the oxygen saturation was decreased in WT mice from day 14 after administration, but maintained at a high level in KO mice. These results suggested that bleomycin-induced inflammatory and pulmonary fibrosis were also attenuated by ACSL4 deficiency.
