{"doi":"10.1152/ajpheart.00921.2003","title":"Radicicol activates heat shock protein expression and cardioprotection in neonatal rat cardiomyocytes","abstract":"<jats:p>Heat shock proteins (HSPs) constitute an endogenous cellular defense mechanism against environmental stresses. In the past few years, studies have shown that overexpression of HSPs can protect cardiac myocytes against ischemia-reperfusion injury. In an attempt to increase the HSPs in cardiac tissue, we used the compound radicicol that activates HSP expression by binding to the HSP 90 kDa (HSP90). HSP90 is the main component of the cytosolic molecular chaperone complex, which has been implicated in the regulation of the heat shock factor 1 (HSF1). HSF1 is responsible for the transcriptional activation of the heat shock genes. In the present study, we show that radicicol induces HSP expression in neonatal rat cardiomyocytes, and this increase in HSPs confers cardioprotection to these cardiomyocytes. We also show that radicicol induction of the HSP and cardioprotection is dependent on the inhibition of HSP90 in cardiomyocytes. These results indicate that modulation of the active HSP90 protein level plays an important role in cardioprotection. Therefore, compounds, such as radicicol and its possible derivatives that inhibit the function of HSP90 in the cell may represent potentially useful cardioprotective agents.</jats:p>","journal":"American Journal of Physiology-Heart and Circulatory Physiology","year":2004,"id":604876,"datarank":2.8601676775409572,"base_score":3.970291913552122,"endowment":3.970291913552122,"self_citation_contribution":0.5955437870328184,"citation_network_contribution":2.264623890508139,"self_endowment_contribution":0.5955437870328184,"citer_contribution":2.264623890508139,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":47,"citers_with_citation_signal":44,"citers_with_endowment":44,"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":1552074,"name":"Tina V. Valdez","orcid":null,"position":1,"is_corresponding":false},{"id":1552076,"name":"Ruben Mestril","orcid":null,"position":2,"is_corresponding":false},{"id":1552071,"name":"Tina M. Griffin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Radicicol activates heat shock protein expression and cardioprotection in neonatal rat cardiomyocytes","abstract":"<jats:p>Heat shock proteins (HSPs) constitute an endogenous cellular defense mechanism against environmental stresses. In the past few years, studies have shown that overexpression of HSPs can protect cardiac myocytes against ischemia-reperfusion injury. In an attempt to increase the HSPs in cardiac tissue, we used the compound radicicol that activates HSP expression by binding to the HSP 90 kDa (HSP90). HSP90 is the main component of the cytosolic molecular chaperone complex, which has been implicated in the regulation of the heat shock factor 1 (HSF1). HSF1 is responsible for the transcriptional activation of the heat shock genes. In the present study, we show that radicicol induces HSP expression in neonatal rat cardiomyocytes, and this increase in HSPs confers cardioprotection to these cardiomyocytes. We also show that radicicol induction of the HSP and cardioprotection is dependent on the inhibition of HSP90 in cardiomyocytes. These results indicate that modulation of the active HSP90 protein level plays an important role in cardioprotection. Therefore, compounds, such as radicicol and its possible derivatives that inhibit the function of HSP90 in the cell may represent potentially useful cardioprotective agents.</jats:p>","is_dataset_classified":null,"base_score":3.970291913552122,"endowment":3.970291913552122,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15117720","pmcid":null,"openalex_id":"https://openalex.org/W2137206941","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL-61339","title":null}],"total_grants":1,"fwci":1.3172,"citation_percentile":0.78774959,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2014,"count":2},{"year":2016,"count":2},{"year":2017,"count":4},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":3},{"year":2021,"count":5},{"year":2022,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.physiology.org/doi/pdf/10.1152/ajpheart.00921.2003","host_type":"publisher"},{"url":"https://doi.org/10.1152/ajpheart.00921.2003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15117720","host_type":"repository"}],"fields_of_study":["Heat shock proteins research","Advanced Thermodynamic Systems and Engines"],"mesh_terms":["Heat Shock Transcription Factors","Animals","Animals, Newborn","Cardiotonic Agents","DNA-Binding Proteins","Heat-Shock Proteins","Humans","Lactones","Transcription Factors","Myocardial Reperfusion Injury","Myocardial Ischemia","Rats, Sprague-Dawley","HSP90 Heat-Shock Proteins","Macrolides","Myocytes, Cardiac","Rats"],"keywords":["Cardioprotection","Hsp90","Heat shock protein","HSF1","Cell biology","Hsp70","Heat shock factor","Chaperone (clinical)","Heat shock","Cytosol","Biology","Myocyte","Endogeny","Chemistry","Ischemia","Medicine","Biochemistry","Gene","Internal medicine","Pathology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T01:06:23.221098Z","pmid":null,"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":[]}