{"doi":"10.3390/ijms23094675","title":"Rotenone-Induced 4-HNE Aggresome Formation and Degradation in HL-1 Cardiomyocytes: Role of Autophagy Flux","abstract":"Reactive oxygen species (ROS) cause oxidative stress by generating reactive aldehydes known as 4-hydroxynonenal (4-HNE). 4-HNE modifies protein via covalent adduction; however, little is known about the degradation mechanism of 4-HNE-adducted proteins. Autophagy is a dynamic process that maintains cellular homeostasis by removing damaged organelles and proteins. In this study, we determined the role of a superoxide dismutase (SOD) mimetic MnTnBuOE-2-PyP5+ (MnP, BMX-001) on rotenone-induced 4-HNE aggresome degradation in HL-1 cardiomyocytes. A rotenone treatment (500 nM) given for 24 h demonstrated both increased ROS and 4-HNE aggresome accumulation in HL-1 cardiomyocytes. In addition, cardiomyocytes treated with rotenone displayed an increase in the autophagy marker LC3-II, as shown by immunoblotting and immunofluorescence. A pre-treatment with MnP (20 µM) for 24 h attenuated rotenone-induced ROS formation. An MnP pre-treatment showed decreased 4-HNE aggresomes and LC3-II formation. A rotenone-induced increase in autophagosomes was attenuated by a pre-treatment with MnP, as shown by fluorescent-tagged LC3 (tfLC3). Rotenone increased tubulin hyperacetylation through the ROS-mediated pathway, which was attenuated by MnP. The disruption of autophagy caused HL-1 cell death because a 3-methyladenine inhibitor of autophagosomes caused reduced cell death. Yet, rapamycin, an inducer of autophagy, increased cell death. These results indicated that a pre-treatment with MnP decreased rotenone-induced 4-HNE aggresomes by enhancing the degradation process.","journal":"International Journal of Molecular Sciences","year":2022,"id":263037,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"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":826994,"name":"Foram Patel","orcid":"0000-0001-9913-2609","position":1,"is_corresponding":false},{"id":293430,"name":"Hosne Ara","orcid":null,"position":2,"is_corresponding":false},{"id":920036,"name":"Ezra Bess","orcid":null,"position":3,"is_corresponding":false},{"id":910687,"name":"Alika Shum","orcid":null,"position":4,"is_corresponding":false},{"id":291376,"name":"Susmita Bhattarai","orcid":"0000-0002-5667-3218","position":5,"is_corresponding":false},{"id":827651,"name":"Utsab Subedi","orcid":"0000-0002-3223-9716","position":6,"is_corresponding":false},{"id":920037,"name":"Daquonte Sanard Bell","orcid":null,"position":7,"is_corresponding":false},{"id":291378,"name":"Md. Shenuarin Bhuiyan","orcid":"0000-0003-0073-3071","position":8,"is_corresponding":false},{"id":291382,"name":"Hong Sun","orcid":"0000-0003-2135-3107","position":9,"is_corresponding":false},{"id":380443,"name":"Ines Batinic̈‐Haberle","orcid":"0000-0001-8037-1861","position":10,"is_corresponding":false},{"id":291383,"name":"Manikandan Panchatcharam","orcid":"0000-0002-7691-8948","position":11,"is_corresponding":false},{"id":291384,"name":"Sumitra Miriyala","orcid":"0000-0001-7158-9295","position":12,"is_corresponding":false},{"id":826993,"name":"Sudha Sharma","orcid":"0000-0002-3359-9545","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:26:29.321923Z","pmid":"35563066","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":[]}