{"doi":"10.1016/j.redox.2020.101625","title":"Specific O-GlcNAc modification at Ser-615 modulates eNOS function","abstract":"Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and devastating disease characterized by vascular smooth muscle and endothelial cell proliferation leading to a narrowing of the vessels in the lung. The increased resistance in the lung and the higher pressures generated result in right heart failure. Nitric Oxide (NO) deficiency is considered a hallmark of IPAH and altered function of endothelial nitric oxide synthase (eNOS), decreases NO production. We recently demonstrated that glucose dysregulation results in augmented protein serine/threonine hydroxyl-linked N-Acetyl-glucosamine (O-GlcNAc) modification in IPAH. In diabetes, dysregulated glucose metabolism has been shown to regulate eNOS function through inhibition of Ser-1177 phosphorylation. However, the link between O-GlcNAc and eNOS function remains unknown. Here we show that increased protein O-GlcNAc occurs on eNOS in PAH and Ser-615 appears to be a novel site of O-GlcNAc modification resulting in reduced eNOS dimerization. Functional characterization of Ser-615 demonstrated the importance of this residue on the regulation of eNOS activity through control of Ser-1177 phosphorylation. Here we demonstrate a previously unidentified regulatory mechanism of eNOS whereby the O-GlcNAc modification of Ser-615 results in reduced eNOS activity and endothelial dysfunction under conditions of glucose dysregulation.","journal":"Redox Biology","year":2020,"id":94830,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":267598,"name":"Jarrod W. Barnes","orcid":"0000-0002-1027-6591","position":1,"is_corresponding":false},{"id":471857,"name":"Liping Tian","orcid":"0000-0003-4280-793X","position":2,"is_corresponding":false},{"id":472532,"name":"Noël E. Mellor","orcid":null,"position":3,"is_corresponding":false},{"id":472533,"name":"Mohammad Mahfuzul Haque","orcid":null,"position":4,"is_corresponding":false},{"id":256163,"name":"Belinda Willard","orcid":"0000-0001-6884-6369","position":5,"is_corresponding":false},{"id":471858,"name":"Ling Li","orcid":"0000-0001-6485-9621","position":6,"is_corresponding":false},{"id":57665,"name":"Suzy Comhair","orcid":"0000-0003-1918-9002","position":7,"is_corresponding":false},{"id":360859,"name":"Dennis J. Stuehr","orcid":"0000-0002-0960-6848","position":8,"is_corresponding":false},{"id":331637,"name":"Raed A. Dweik","orcid":"0000-0002-4425-1288","position":9,"is_corresponding":false},{"id":362779,"name":"Kulwant S. Aulak","orcid":null,"position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:33:00.770265Z","pmid":"32863226","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":[]}