{"doi":"10.1016/j.jlr.2022.100179","title":"Neutral ceramidase deficiency protects against cisplatin-induced acute kidney injury","abstract":"Cisplatin is a commonly used chemotherapeutic for the treatment of many solid organ cancers; however, its effectiveness is limited by the development of acute kidney injury (AKI) in 30% of patients. AKI is driven by proximal tubule cell death, leading to rapid decline in renal function. It has previously been shown that sphingolipid metabolism plays a role in regulating many of the biological processes involved in cisplatin-induced AKI. For example, neutral ceramidase (nCDase) is an enzyme responsible for converting ceramide into sphingosine, which is then phosphorylated to become sphingosine-1-phosphate, and our lab previously demonstrated that nCDase knockout (nCDase-/-) in mouse embryonic fibroblasts led to resistance to nutrient and energy deprivation-induced cell death via upregulation of autophagic flux. In this study, we further characterized the role of nCDase in AKI by demonstrating that nCDase-/- mice are resistant to cisplatin-induced AKI. nCDase-/- mice display improved kidney function, reduced injury and structural damage, lower rates of apoptosis, and less ER stress compared to wild-type mice following cisplatin treatment. Although the mechanism of protection is still unknown, we propose that it could be mediated by increased autophagy, as chloroquine treatment resensitized nCDase-/- mice to AKI development. Taken together, we conclude that nCDase may represent a novel target to prevent cisplatin-induced nephrotoxicity.","journal":"Journal of Lipid Research","year":2022,"id":271449,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":936832,"name":"Tess V. Dupre","orcid":"0000-0002-6912-3194","position":1,"is_corresponding":false},{"id":343437,"name":"Parag P. Shah","orcid":null,"position":2,"is_corresponding":false},{"id":461764,"name":"Deanna Davis","orcid":"0000-0003-3637-1973","position":3,"is_corresponding":false},{"id":117877,"name":"Mark A. Doll","orcid":null,"position":4,"is_corresponding":false},{"id":937374,"name":"Cierra N. Sharp","orcid":null,"position":5,"is_corresponding":false},{"id":880093,"name":"Alexis A. Vega","orcid":"0000-0002-9359-6880","position":6,"is_corresponding":false},{"id":491475,"name":"Judit Megyesi","orcid":null,"position":7,"is_corresponding":false},{"id":342348,"name":"Levi J. Beverly","orcid":"0000-0003-4652-4881","position":8,"is_corresponding":false},{"id":316842,"name":"Ashley J. Snider","orcid":"0000-0002-1515-4171","position":9,"is_corresponding":false},{"id":146071,"name":"Lina M. Obeid","orcid":null,"position":10,"is_corresponding":false},{"id":271166,"name":"Yusuf A. Hannun","orcid":"0000-0003-3349-3369","position":11,"is_corresponding":false},{"id":342347,"name":"Leah J. Siskind","orcid":"0000-0001-5026-5187","position":12,"is_corresponding":false},{"id":936831,"name":"Sophia M. Sears","orcid":"0000-0003-2396-5385","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:27:39.717534Z","pmid":"35151662","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}