{"id":"https://openalex.org/W4408968356","doi":"https://doi.org/10.1016/j.ejphar.2025.177549","title":"Donepezil-induced degradation of hERG potassium channel via lysosomal pathway is exacerbated by hypoxia","display_name":"Donepezil-induced degradation of hERG potassium channel via lysosomal pathway is exacerbated by hypoxia","publication_year":2025,"publication_date":"2025-03-29","ids":{"openalex":"https://openalex.org/W4408968356","doi":"https://doi.org/10.1016/j.ejphar.2025.177549","pmid":"https://pubmed.ncbi.nlm.nih.gov/40157707"},"language":"en","primary_location":{"id":"doi:10.1016/j.ejphar.2025.177549","doi":"https://doi.org/10.1016/j.ejphar.2025.177549","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.ejphar.2025.177549","pdf_url":null,"source":{"id":"https://openalex.org/S187816532","display_name":"European Journal of Pharmacology","issn_l":"0014-2999","issn":["0014-2999","1879-0712"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-d","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"European Journal of Pharmacology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1016/j.ejphar.2025.177549","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5027761713","display_name":"Yuexin Li","orcid":"https://orcid.org/0000-0001-7772-8743","observed_orcids":["https://orcid.org/0000-0001-7772-8743","https://orcid.org/0000-0001-8525-2853"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yuexin Li","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Jinyang Sun","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jinyang Sun","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100758188","display_name":"Xiaoxu Li","orcid":"https://orcid.org/0000-0002-3778-3964","observed_orcids":["https://orcid.org/0000-0002-3778-3964"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiaoxu Li","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Wenting Yu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Wenting Yu","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016787829","display_name":"Jiacheng Ren","orcid":"https://orcid.org/0009-0001-5823-9407","observed_orcids":["https://orcid.org/0009-0001-5823-9407"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jiacheng Ren","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Baoqiang Wang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Baoqiang Wang","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100567631","display_name":"Han Xiaoxia","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiaoxia Han","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Lu Ma","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Lu Ma","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Xiang Sun","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiang Sun","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Wei Teng","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Wei Teng","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101998993","display_name":"Xueping Gu","orcid":"https://orcid.org/0000-0001-9575-7089","observed_orcids":["https://orcid.org/0000-0001-9575-7089"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiwei Gu","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Qirui Ding","orcid":"https://orcid.org/0009-0007-0967-2099","observed_orcids":["https://orcid.org/0009-0007-0967-2099"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Qirui Ding","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China"],"raw_orcid":"https://orcid.org/0009-0007-0967-2099","affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5101620548","display_name":"Baoxin Li","orcid":"https://orcid.org/0000-0002-1680-3970","observed_orcids":["https://orcid.org/0000-0002-1680-3970"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Baoxin Li","raw_affiliation_strings":["Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: libaoxin@ems.hrbmu.edu.cn"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: libaoxin@ems.hrbmu.edu.cn","institution_ids":["https://openalex.org/I156144747"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5101620548"],"corresponding_institution_ids":["https://openalex.org/I156144747"],"apc_list":{"value":3230,"currency":"USD","value_usd":3230},"apc_paid":{"value":3230,"currency":"USD","value_usd":3230},"fwci":1.8982,"has_fulltext":false,"cited_by_count":3,"citation_normalized_percentile":{"value":0.85666955,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":97,"max":98},"biblio":{"volume":"996","issue":null,"first_page":"177549","last_page":"177549"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.9961000084877014,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.9961000084877014,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10493","display_name":"Ion channel regulation and function","score":0.002099999925121665,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10724","display_name":"Ion Transport and Channel Regulation","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/donepezil","display_name":"donepezil","score":0.9940000176429749},{"id":"https://openalex.org/keywords/herg-channel","display_name":"hERG","score":0.9810000061988831},{"id":"https://openalex.org/keywords/lysosomal-degradation","display_name":"lysosomal degradation","score":0.7670000195503235},{"id":"https://openalex.org/keywords/hypoxia","display_name":"hypoxia","score":0.9710000157356262},{"id":"https://openalex.org/keywords/long-qt-syndrome","display_name":"long QT syndrome","score":0.6570000052452087},{"id":"https://openalex.org/keywords/drug-induced-cardiotoxicity","display_name":"drug-induced cardiotoxicity","score":0.7929999828338623},{"id":"https://openalex.org/keywords/protein-stability","display_name":"protein stability","score":0.625},{"id":"https://openalex.org/keywords/acetylation","display_name":"acetylation","score":0.6179999709129333},{"id":"https://openalex.org/keywords/ubiquitination","display_name":"ubiquitination","score":0.9929999709129333},{"id":"https://openalex.org/keywords/hdac6","display_name":"HDAC6","score":0.9549999833106995},{"id":"https://openalex.org/keywords/chmp3","display_name":"CHMP3","score":0.8080000281333923},{"id":"https://openalex.org/keywords/escrt-iii","display_name":"ESCRT-III","score":0.9710000157356262},{"id":"https://openalex.org/keywords/rab11","display_name":"Rab11","score":0.9559999704360962},{"id":"https://openalex.org/keywords/endocytosis","display_name":"endocytosis","score":0.8830000162124634},{"id":"https://openalex.org/keywords/action-potential-duration","display_name":"action potential duration","score":0.5809999704360962},{"id":"https://openalex.org/keywords/cardiac-arrhythmia","display_name":"cardiac arrhythmias","score":0.6850000023841858},{"id":"https://openalex.org/keywords/human-induced-pluripotent-stem-cell-derived-cardiomyocytes","display_name":"human induced pluripotent stem cell-derived cardiomyocytes","score":0.8309999704360962}],"concepts":[{"id":"https://openalex.org/C2779362680","wikidata":"https://www.wikidata.org/wiki/Q905000","display_name":"hERG","level":3,"score":0.9134265780448914},{"id":"https://openalex.org/C7836513","wikidata":"https://www.wikidata.org/wiki/Q1641506","display_name":"Hypoxia (environmental)","level":3,"score":0.6435856819152832},{"id":"https://openalex.org/C83743174","wikidata":"https://www.wikidata.org/wiki/Q423778","display_name":"Potassium channel","level":2,"score":0.6034097671508789},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.5295126438140869},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5079565644264221},{"id":"https://openalex.org/C2780904820","wikidata":"https://www.wikidata.org/wiki/Q415081","display_name":"Donepezil","level":4,"score":0.46243202686309814},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.27462905645370483},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.2487356960773468},{"id":"https://openalex.org/C540031477","wikidata":"https://www.wikidata.org/wiki/Q629","display_name":"Oxygen","level":2,"score":0.09072321653366089},{"id":"https://openalex.org/C2779483572","wikidata":"https://www.wikidata.org/wiki/Q83030","display_name":"Dementia","level":3,"score":0.0},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000072237","descriptor_name":"ERG1 Potassium Channel","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000072237","descriptor_name":"ERG1 Potassium Channel","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000073864","descriptor_name":"Histone Deacetylase 6","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000073864","descriptor_name":"Histone Deacetylase 6","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000077265","descriptor_name":"Donepezil","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000077265","descriptor_name":"Donepezil","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000077265","descriptor_name":"Donepezil","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000077265","descriptor_name":"Donepezil","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000107","descriptor_name":"Acetylation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000107","descriptor_name":"Acetylation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000200","descriptor_name":"Action Potentials","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000200","descriptor_name":"Action Potentials","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004705","descriptor_name":"Endocytosis","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D004705","descriptor_name":"Endocytosis","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D006168","descriptor_name":"Guinea Pigs","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006168","descriptor_name":"Guinea Pigs","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008133","descriptor_name":"Long QT Syndrome","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":false},{"descriptor_ui":"D008133","descriptor_name":"Long QT Syndrome","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":false},{"descriptor_ui":"D008133","descriptor_name":"Long QT Syndrome","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008133","descriptor_name":"Long QT Syndrome","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008247","descriptor_name":"Lysosomes","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D008247","descriptor_name":"Lysosomes","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D008247","descriptor_name":"Lysosomes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D008247","descriptor_name":"Lysosomes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015687","descriptor_name":"Cell Hypoxia","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D015687","descriptor_name":"Cell Hypoxia","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D032383","descriptor_name":"Myocytes, Cardiac","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D032383","descriptor_name":"Myocytes, Cardiac","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D032383","descriptor_name":"Myocytes, Cardiac","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D032383","descriptor_name":"Myocytes, Cardiac","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D054875","descriptor_name":"Ubiquitination","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D054875","descriptor_name":"Ubiquitination","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D057026","descriptor_name":"Induced Pluripotent Stem Cells","qualifier_ui":"Q000166","qualifier_name":"cytology","is_major_topic":false},{"descriptor_ui":"D057026","descriptor_name":"Induced Pluripotent Stem Cells","qualifier_ui":"Q000166","qualifier_name":"cytology","is_major_topic":false},{"descriptor_ui":"D057026","descriptor_name":"Induced Pluripotent Stem Cells","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D057026","descriptor_name":"Induced Pluripotent Stem Cells","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D057026","descriptor_name":"Induced Pluripotent Stem Cells","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D057026","descriptor_name":"Induced Pluripotent Stem Cells","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D059748","descriptor_name":"Proteolysis","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D059748","descriptor_name":"Proteolysis","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1016/j.ejphar.2025.177549","doi":"https://doi.org/10.1016/j.ejphar.2025.177549","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.ejphar.2025.177549","pdf_url":null,"source":{"id":"https://openalex.org/S187816532","display_name":"European Journal of Pharmacology","issn_l":"0014-2999","issn":["0014-2999","1879-0712"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-d","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"European Journal of Pharmacology","raw_type":"journal-article"},{"id":"pmid:40157707","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40157707","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"European journal of pharmacology","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1016/j.ejphar.2025.177549","doi":"https://doi.org/10.1016/j.ejphar.2025.177549","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.ejphar.2025.177549","pdf_url":null,"source":{"id":"https://openalex.org/S187816532","display_name":"European Journal of Pharmacology","issn_l":"0014-2999","issn":["0014-2999","1879-0712"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-d","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"European Journal of Pharmacology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9940000176429749,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[{"score":0.5299999713897705,"id":"https://metadata.un.org/sdg/6","display_name":"Clean water and sanitation"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G5634417316","display_name":null,"funder_award_id":"LH2022H014","funder_id":"https://openalex.org/F4320323085","funder_display_name":"Natural Science Foundation of Heilongjiang Province"},{"id":"https://openalex.org/G7306878872","display_name":null,"funder_award_id":"82274029","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"}],"funders":[{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320323085","display_name":"Natural Science Foundation of Heilongjiang Province","ror":null}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":37,"referenced_works":["https://openalex.org/W1152283192","https://openalex.org/W1726172583","https://openalex.org/W1853984831","https://openalex.org/W1974298740","https://openalex.org/W2017425965","https://openalex.org/W2031700109","https://openalex.org/W2032656914","https://openalex.org/W2039193707","https://openalex.org/W2050339689","https://openalex.org/W2060867941","https://openalex.org/W2085682841","https://openalex.org/W2093266648","https://openalex.org/W2100004795","https://openalex.org/W2119442825","https://openalex.org/W2164642232","https://openalex.org/W2299874350","https://openalex.org/W2560345632","https://openalex.org/W2745072699","https://openalex.org/W2792198857","https://openalex.org/W2886609030","https://openalex.org/W2916086478","https://openalex.org/W2998246270","https://openalex.org/W3002146777","https://openalex.org/W3023371135","https://openalex.org/W3045338643","https://openalex.org/W3047388418","https://openalex.org/W3053281893","https://openalex.org/W3087191797","https://openalex.org/W3135480446","https://openalex.org/W3141330997","https://openalex.org/W3197054512","https://openalex.org/W3197243128","https://openalex.org/W4226160697","https://openalex.org/W4285500368","https://openalex.org/W4377289384","https://openalex.org/W4391172284","https://openalex.org/W6803875031"],"related_works":["https://openalex.org/W2039193707","https://openalex.org/W2902463392","https://openalex.org/W2224561562","https://openalex.org/W2385176120","https://openalex.org/W2477223983","https://openalex.org/W2566712748","https://openalex.org/W2388409414","https://openalex.org/W1964429833","https://openalex.org/W2081363492","https://openalex.org/W2004143214"],"abstract_inverted_index":{"/hERG,":[0],"which":[1],"is":[2],"essential":[3],"for":[4],"cardiac":[5],"repolarization.":[6],"This":[7],"study":[8],"aimed":[9],"to":[10,39,47,66,199,202],"investigate":[11],"DPZ's":[12],"effect":[13],"on":[14,23],"hERG":[15,49,92,107,115,123,134,161,174,209],"channel":[16],"and":[17,51,77,95,110,120,143,163,169],"its":[18,181],"cardiotoxic":[19],"mechanism,":[20],"particularly":[21],"focusing":[22],"whether":[24],"hypoxia":[25],"increases":[26],"the":[27,43,52,98,112,121,178,188],"risk":[28,189],"of":[29,55,114,151,190,208],"DPZ-induced":[30,160],"acLQTS.":[31],"To":[32],"explore":[33],"these,":[34],"we":[35],"employed":[36],"western":[37],"blotting":[38],"analyze":[40],"protein":[41,93,108,124,136,150,175],"levels,":[42],"patch":[44],"clamp":[45],"technique":[46],"measure":[48],"current":[50,96],"action":[53],"potentials":[54],"human-induced":[56],"pluripotent":[57],"stem":[58],"cell-derived":[59],"cardiomyocytes":[60],"(hiPSC-CMs).":[61],"Additionally,":[62],"immunoprecipitation":[63],"was":[64,125],"utilized":[65],"detect":[67],"protein-protein":[68],"interactions.":[69],"Finally,":[70],"optical":[71],"mapping":[72],"monitored":[73],"guinea":[74,167],"pig":[75],"ECGs":[76],"APD,":[78],"providing":[79],"in":[80,97,106,166,177,183,210],"vivo":[81],"insights.":[82],"Our":[83],"results":[84],"indicate":[85],"that":[86],"24-h":[87],"incubation":[88],"with":[89],"DPZ":[90,102,132,172,206],"inhibits":[91],"levels":[94],"plasma":[99],"membrane.":[100],"Mechanistically,":[101],"induces":[103],"an":[104],"imbalance":[105],"acetylation/ubiquitination":[109],"decreases":[111],"stability":[113,176],"by":[116,193,205],"promoting":[117,180],"HDAC6":[118],"expression,":[119],"ubiquitinated":[122],"degraded":[126],"at":[127],"lysosomes":[128],"via":[129,137,146],"K63-polyubiquitin":[130],"chains.":[131],"affects":[133],"membrane":[135],"two":[138],"pathways:":[139],"it":[140],"accelerates":[141],"endocytosis":[142],"directs":[144],"degradation":[145,162,182],"CHMP3":[147],"(a":[148],"sorting":[149],"ESCRT-III),":[152],"while":[153],"inhibiting":[154],"recycling":[155],"through":[156],"Rab11.":[157],"Hypoxia":[158,185],"exacerbates":[159,187],"APD":[164],"prolongation":[165],"pigs":[168],"hiPSC-CMs.":[170],"Collectively,":[171],"reduces":[173],"membrane,":[179],"lysosomes.":[184],"further":[186],"arrhythmia":[191],"caused":[192],"DPZ.":[194],"These":[195],"findings":[196],"remind":[197],"us":[198],"pay":[200],"attention":[201],"acLQTS":[203],"induced":[204],"inhibition":[207],"clinical":[211],"applications.":[212]},"counts_by_year":[{"year":2026,"cited_by_count":3}],"updated_date":"2026-10-16T09:59:22.235173","created_date":"2025-10-10T00:00:00"}