Gene deletion of long-chain acyl-CoA synthetase 4 attenuates xenobiotic chemical-induced lung injury via the suppression of lipid peroxidation.

ABSTRACT: Long-chain acyl-CoA synthetase (ACSL) 4 converts polyunsaturated fatty acids (PUFAs) into their acyl-CoAs and plays an important role in maintaining PUFA-containing membrane phospholipids. Here we demonstrated decreases in various kinds of PUFA-containing phospholipid species in ACSL4-deficient murine lung. We then examined the effects of ACSL4 gene deletion on lung injury by treating mice with two pulmonary toxic chemicals: paraquat (PQ) and methotrexate (MTX). The results showed that ACSL4 deficiency attenuated PQ-induced acute lung lesion and decreased mortality. PQ-induced lung inflammation and neutrophil migration were also suppressed in ACSL4-deficient mice. PQ administration increased the levels of phospholipid hydroperoxides in the lung, but ACSL4 gene deletion suppressed their inc

SUBMITTER: Tomitsuka Y 

PROVIDER: S-EPMC10450978 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature