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http://purl.uniprot.org/citations/36916093http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36916093http://www.w3.org/2000/01/rdf-schema#comment"

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.

Methods

HK-2 cells were challenged with LPS to construct a model of sepsis-induced AKI in 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.

Results

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.

Conclusion

CHAC1 exacerbated ferroptosis and apoptosis by enhancing oxidative stress in LPS-induced HK-2 cells."xsd:string
http://purl.uniprot.org/citations/36916093http://purl.org/dc/terms/identifier"doi:10.15586/aei.v51i2.760"xsd:string
http://purl.uniprot.org/citations/36916093http://purl.uniprot.org/core/author"Zhou Z."xsd:string
http://purl.uniprot.org/citations/36916093http://purl.uniprot.org/core/author"Zhang H."xsd:string
http://purl.uniprot.org/citations/36916093http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36916093http://purl.uniprot.org/core/name"Allergol Immunopathol (Madr)"xsd:string
http://purl.uniprot.org/citations/36916093http://purl.uniprot.org/core/pages"99-110"xsd:string
http://purl.uniprot.org/citations/36916093http://purl.uniprot.org/core/title"CHAC1 exacerbates LPS-induced ferroptosis and apoptosis in HK-2 cells by promoting oxidative stress."xsd:string
http://purl.uniprot.org/citations/36916093http://purl.uniprot.org/core/volume"51"xsd:string
http://purl.uniprot.org/citations/36916093http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36916093
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