| First Author | Tomitsuka Y | Year | 2023 |
| Journal | Redox Biol | Volume | 66 |
| Pages | 102850 | PubMed ID | 37586249 |
| Mgi Jnum | J:339279 | Mgi Id | MGI:7521458 |
| Doi | 10.1016/j.redox.2023.102850 | Citation | Tomitsuka Y, et al. (2023) Gene deletion of long-chain acyl-CoA synthetase 4 attenuates xenobiotic chemical-induced lung injury via the suppression of lipid peroxidation. Redox Biol 66:102850 |
| abstractText | 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 increment. We further found that ACSL4 deficiency attenuated MTX-induced pulmonary fibrosis. These results suggested that ACSL4 gene deletion might confer protection against pulmonary toxic chemical-induced lung injury by reducing PUFA-containing membrane phospholipids, leading to the suppression of lipid peroxidation. Inhibition of ACSL4 may be promising for the prevention and treatment of chemical-induced lung injury. |
