{"doi":"10.1515/bc.2005.077","title":"Inhibition of aldosterone biosynthesis by staurosporine","abstract":"<jats:title>Abstract</jats:title><jats:p>Staurosporine (STS) is a very potent broad-range kinase inhibitor, and its antiproliferative properties made it a lead compound for protein kinase C (PKC) inhibitors with therapeutic potential. Because STS also causes hypotension, we investigated in this study whether it directly interferes with the terminal steps of aldosterone biosynthesis; these are catalysed by a mitochondrial steroid hydroxylase system consisting of adrenodoxin reductase, adrenodoxin, and the cytochrome P450 enzyme hCYP11B2 (aldosterone synthase). Here we demonstrate that nanomolar concentrations of STS significantly reduced aldosterone synthase activity in transiently transfected COS-1 cells and in stably transfected V79MZh11B2 cells (IC<jats:sub>50</jats:sub>=11 nM). However, STS did not inhibit bovine aldosterone synthase in a reconstituted steroid hydroxylation assay. In transiently transfected COS-1 cells, the protein level of adrenodoxin (but not that of adrenodoxin reductase or of hCYP11B2) was significantly reduced after treatment with 2 nM STS. Finally, we show that STS treatment (1 μg/day) of mice reduced their aldosterone/renin ratio by almost 50% (<jats:italic>p</jats:italic>=0.015). To the best of our knowledge, this is the first report of a direct<jats:italic>in vivo</jats:italic>effect of STS on the renin-angiotensin-aldosterone system. We conclude (i) that the hypotensive effect of staurosporine is at least partly due to inhibition of aldosterone biosynthesis via adrenodoxin depletion, and (ii) that aldosterone biosynthesis can be regulated<jats:italic>in vivo</jats:italic>at the level of adrenodoxin availability.</jats:p>","journal":"Biological Chemistry","year":2005,"id":36341,"datarank":0.24645582796459647,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.038511673796612855,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.038511673796612855,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"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":184281,"name":"Alexander Mion","orcid":null,"position":1,"is_corresponding":false},{"id":184282,"name":"Christopher J. Kenyon","orcid":null,"position":2,"is_corresponding":false},{"id":184247,"name":"Rita Bernhardt","orcid":null,"position":3,"is_corresponding":false},{"id":184280,"name":"Matthias Bureik","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16207087","pmcid":null,"openalex_id":"https://openalex.org/W2009949838","authors":[],"funders":[],"total_grants":0,"fwci":0.1575,"citation_percentile":0.54442246,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2018,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://www.degruyter.com/view/j/bchm.2005.386.issue-7/bc.2005.077/bc.2005.077.xml","host_type":"publisher"},{"url":"https://www.degruyter.com/document/doi/10.1515/BC.2005.077/pdf","host_type":"publisher"},{"url":"https://doi.org/10.1515/bc.2005.077","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16207087","host_type":"repository"}],"fields_of_study":["Hormonal Regulation and Hypertension","Pharmacogenetics and Drug Metabolism","Estrogen and related hormone effects","Chemistry","Medicine","Aldosterone","Animals","COS Cells","Cytochrome P-450 CYP11B2","Female","Humans","Male","Mice","Mice, Inbred C57BL","Staurosporine","Steroid 11-beta-Hydroxylase","Steroid Hydroxylases","Transfection"],"mesh_terms":["Aldosterone","Animals","Female","Humans","Male","Mice, Inbred C57BL","Steroid Hydroxylases","Steroid 11-beta-Hydroxylase","Transfection","Staurosporine","Cytochrome P-450 CYP11B2","COS Cells","Mice"],"keywords":["Adrenodoxin","Aldosterone","Staurosporine","Aldosterone synthase","Steroid 11-beta-hydroxylase","Chemistry","Mineralocorticoid","Renin–angiotensin system","Biosynthesis","Biochemistry","Endocrinology","Internal medicine","Enzyme","Cytochrome P450","Protein kinase C","Steroid","Biology","Medicine","Hormone"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T15:41:00.054243Z","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":[]}