{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:41:26Z","timestamp":1789792886437,"version":"4.0.1"},"reference-count":0,"publisher":"Codon Publications","issue":"2","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergol Immunopathol"],"abstract":"<jats:p>Background: Sepsis-induced acute kidney injury (AKI) is a singularly grievous and life-threatening syndrome. Its pathogenesis is closely related to inflammatory response, apoptosis, oxidative stress, and ferroptosis. Cation transport regulator-like protein 1 (CHAC1), as a proapoptic factor, may be involved in apoptosis, oxidative stress, and ferroptosis. This study aimed to explore the role of CHAC1 in the lipopolysaccharide (LPS)-induced the human renal proximal tubular epithelial (HK-2) cells.\nMethods: HK-2 cells were challenged with LPS to construct a model of sepsis-induced AKI\u00a0in vitro. The role of CHAC1 in the LPS-induced HK-2 cells was explored using Western blot assay, cell counting kit-8 (CCK-8), flow cytometry, and colorimetric assays. Additionally, N-acetyl cysteine (NAC) was incubated with HK-2 cells to define deeply the relation between oxidative stress and apoptosis or ferroptosis.\nResults: The expression of CHAC1 was enhanced in the kidney tissues of mice with sepsis--induced multiple organ dysfunction syndrome (MODS), through the Gene Expression Omnibus database (GSE60088 microarray dataset), and in the LPS-induced HK-2 cells. The cell viability was significantly reduced by LPS treatment, which was at least partly restored by the transfection of siCHAC1#1 and siCHAC1#2 but not siNC. In addition, down-regulation of CHAC1 counteracted the LPS-induced reactive oxygen species level and malonaldehyde concentrations while restored the LPS-induced glutathione concentrations. Meanwhile, interference of CHAC1 neutralized LPS-induced apoptosis rate, and the relative level of cleaved poly(ADP-ribose) polymerase (PARP)\/PARP, and cleaved caspase-3\/caspase-3. In addition, silencing of CHAC1 recovered the LPS-induced enhanced protein level of glutathione peroxidase 4 (GPx4) whereas antagonized the LPS-induced relative protein level of ACSL4 and that of iron. Moreover, application of NAC inverted the effect of CHAC1 on apoptosis and ferroptosis in HK-2 cells.\nConclusion: CHAC1 exacerbated ferroptosis and apoptosis by enhancing oxidative stress in LPS-induced HK-2 cells.<\/jats:p>","DOI":"10.15586\/aei.v51i2.760","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T12:54:34Z","timestamp":1678107274000},"page":"99-110","source":"Crossref","is-referenced-by-count":28,"title":["CHAC1 exacerbates LPS-induced ferroptosis and apoptosis in HK-2 cells by promoting oxidative stress"],"prefix":"10.15586","volume":"51","author":[{"given":"Zhihui","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6228","published-online":{"date-parts":[[2023,3,1]]},"container-title":["Allergologia et Immunopathologia"],"original-title":[],"link":[{"URL":"https:\/\/all-imm.com\/index.php\/aei\/article\/download\/760\/1207","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/all-imm.com\/index.php\/aei\/article\/download\/760\/1209","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/all-imm.com\/index.php\/aei\/article\/download\/760\/1208","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/all-imm.com\/index.php\/aei\/article\/download\/760\/1207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T12:54:35Z","timestamp":1678107275000},"score":1,"resource":{"primary":{"URL":"https:\/\/all-imm.com\/index.php\/aei\/article\/view\/760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,1]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,3,1]]}},"URL":"https:\/\/doi.org\/10.15586\/aei.v51i2.760","relation":{},"ISSN":["0301-0546"],"issn-type":[{"value":"0301-0546","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,1]]}}}