{"doi":"10.1371/journal.pone.0062968","title":"Ceramide Synthases Expression and Role of Ceramide Synthase-2 in the Lung: Insight from Human Lung Cells and Mouse Models","abstract":null,"journal":"PLoS ONE","year":2013,"id":605948,"datarank":0.6663976884735476,"base_score":4.442651256490317,"endowment":4.442651256490317,"self_citation_contribution":0.6663976884735476,"citation_network_contribution":0.0,"self_endowment_contribution":0.6663976884735476,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":84,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1555364,"name":"Krzysztof Kamocki","orcid":null,"position":1,"is_corresponding":false},{"id":1555365,"name":"Christophe Poirier","orcid":null,"position":2,"is_corresponding":false},{"id":1555366,"name":"Yael Pewzner-Jung","orcid":null,"position":3,"is_corresponding":false},{"id":1555367,"name":"Elad L. 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However, the role of individual ceramide species, or of the enzymes that are responsible for their synthesis, in lung health and disease has not been clarified. We now show that C24- and C16-ceramides are the most abundant lung ceramide species, paralleled by high expression of their synthetic enzymes, ceramide synthase 2 (CerS2) and CerS5, respectively. Furthermore, the ceramide species synthesis in the lung is homeostatically regulated, since mice lacking very long acyl chain C24-ceramides due to genetic deficiency of CerS2 displayed a ten-fold increase in C16-ceramides and C16-dihydroceramides along with elevation of acid sphingomyelinase and CerS5 activities. Despite relatively preserved total lung ceramide levels, inhibition of de novo sphingolipid synthesis at the level of CerS2 was associated with significant airflow obstruction, airway inflammation, and increased lung volumes. Our results suggest that ceramide species homeostasis is crucial for lung health and that CerS2 dysfunction may predispose to inflammatory airway and airspace diseases.","is_dataset_classified":null,"base_score":4.442651256490317,"endowment":4.442651256490317,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23690971","pmcid":"PMC3653891","openalex_id":"https://openalex.org/W2026063366","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"R01HL077328","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL105772","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01HL077328-07","title":"Ceramide-induced lung destruction in emphysema"}],"total_grants":3,"fwci":2.6139,"citation_percentile":0.90042543,"influential_citations":0,"citation_trend":[{"year":2013,"count":2},{"year":2014,"count":6},{"year":2015,"count":8},{"year":2016,"count":3},{"year":2017,"count":8},{"year":2018,"count":6},{"year":2019,"count":7},{"year":2020,"count":10},{"year":2021,"count":8},{"year":2022,"count":7},{"year":2023,"count":10},{"year":2024,"count":2},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0062968&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0062968&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0062968","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0062968","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23690971","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.780.281","host_type":""},{"url":"https://doaj.org/article/34e170a9c540460bb459a106214234dc","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3653891","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3653891","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3653891?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0062968","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0062968","host_type":""}],"fields_of_study":["Sphingolipid Metabolism and Signaling","Carbohydrate Chemistry and Synthesis","Ion Transport and Channel Regulation","0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Animals","Cell Line","Ceramides","Female","Homeostasis","Humans","Lung","Male","Membrane Proteins","Pulmonary Alveoli","Gene Expression Regulation, Enzymologic","Tumor Suppressor Proteins","Sphingosine N-Acyltransferase","Mice"],"keywords":["Ceramide","Ceramide synthase","Sphingolipid","Sphingomyelin","Lipid signaling","Sphingosine","Biology","Lung","Sphingomyelin phosphodiesterase","Acid sphingomyelinase","Inflammation","Immunology","Biochemistry","Internal medicine","Medicine","Male","Science","Tumor Suppressor Proteins","Q","R","Membrane Proteins","Ceramides","Gene Expression Regulation, Enzymologic","Cell Line","Pulmonary Alveoli","Mice","Sphingosine N-Acyltransferase","Animals","Homeostasis","Humans","Female","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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