ArticleCirculation. Cardiovascular genetics2015
Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated by CYP27A1 via Bile Acid Pathway.
Article in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Autonomic activity and its relationship with the endogenous cardiotonic steroid marinobufagenin: the African-PREDICT study.Nutritional neuroscience · 2020Trial
- Functional characterization of 3β-hydroxysteroid dehydrogenases in Asiatic toad reveals an efficient broad substrate specificity of Bg-3βHSD2.Bioscience reports · 2026Article
- Adrenal High-Expressional CYP27A1 Mediates Bile Acid Increase and Functional Impairment in Adult Male Offspring by Prenatal Dexamethasone Exposure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Antibody to Endogenous Cardiotonic Steroid Reverses Vascular Fibrosis and Restores Vasorelaxation in Chronic Kidney Disease.International journal of molecular sciences · 2024Article
- Identifying toxic effects and metabolic perturbations ofToxicology research · 2024Article
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- Pharmacogenomic analysis in adrenocortical carcinoma reveals genetic features associated with mitotane sensitivity and potential therapeutics.Frontiers in endocrinology · 2024Article
- Endogenous Digitalis-like Factors as a Key Molecule in the Pathophysiology of Pregnancy-Induced Hypertension and a Potential Therapeutic Target in Preeclampsia.International journal of molecular sciences · 2023Review
- New Insights on the Role of Marinobufagenin from Bench to Bedside in Cardiovascular and Kidney Diseases.International journal of molecular sciences · 2023Review
- Does the Glucocorticoid Stress Response Make Toads More Toxic? An Experimental Study on the Regulation of Bufadienolide Toxin Synthesis.Integrative organismal biology (Oxford, England) · 2023Article
- The NaFrontiers in endocrinology · 2023Review
- The association of serum total bile acid with new-onset hypertension during pregnancy.BMC pregnancy and childbirth · 2022Article
- Effect of Cardiotonic Steroid Marinobufagenin on Vascular Remodeling and Cognitive Impairment in Young Dahl-S Rats.International journal of molecular sciences · 2022Article
- Canrenone Restores Vasorelaxation Impaired by Marinobufagenin in Human Preeclampsia.International journal of molecular sciences · 2022Article
- Transcriptome Analysis and Identification of the Cholesterol Side Chain Cleavage Enzyme BbgCYP11A1 FromFrontiers in genetics · 2022Article
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- Preeclampsia: Cardiotonic Steroids, Fibrosis, Fli1 and Hint to Carcinogenesis.International journal of molecular sciences · 2021Review
- The Cardiotonic Steroid Marinobufagenin Is a Predictor of Increased Left Ventricular Mass in Obesity: The African-PREDICT Study.Nutrients · 2020Article
- Gut microbiota metabolites as integral mediators in cardiovascular diseases (Review).International journal of molecular medicine · 2020Review
- NaInternational journal of molecular sciences · 2020Article
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9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe bioactive steroid, marinobufagenin, is an endogenous Na/K-ATPase bufadienolide inhibitor that is synthesized by adrenocortical and placental cells. Marinobufagenin binding to Na/K-ATPase initiates profibrotic cell signaling, and heightened marinobufagenin levels are implicated in the pathogenesis of hypertension, preeclampsia, and chronic kidney disease. Steroids are derived from cholesterol through the traditional steroidogenesis pathway initiated by enzyme CYP11A1, and via the acidic bile acid pathway, which is controlled by enzyme CYP27A1. The mechanism of marinobufagenin biosynthesis in mammals, however, remains unknown. METHODS AND
resultsHere, we show that post-transcriptional silencing of the CYP27A1 gene in human trophoblast and rat adrenocortical cells reduced the expression of CYP27A1 mRNA by 70%, reduced total bile acids 2-fold, and marinobufagenin levels by 67% when compared with nontreated cells or cells transfected with nontargeting siRNA. In contrast, silencing of the CYP11A1 gene did not affect marinobufagenin production in either cell culture, but suppressed production of progesterone 2-fold in human trophoblast cells and of corticosterone by 90% in rat adrenocortical cells when compared with cells transfected with nontargeting siRNA. In vivo, in a high-salt administration experiment, male and female Dahl salt-sensitive rats became hypertensive after 4 weeks on a high-NaCl diet, their plasma marinobufagenin levels doubled, and adrenocortical CYP27A1 mRNA and protein increased 1.6-fold and 2.0-fold.
conclusionsTherefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases.
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