Academic Journal
Reprogrammed Propionate Metabolism Alters Redox-Dependent Aldosterone Production.
| Τίτλος: | Reprogrammed Propionate Metabolism Alters Redox-Dependent Aldosterone Production. |
|---|---|
| Συγγραφείς: | Sun M; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China., Gao M; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China., Liu Y; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China., Xia Z; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China., Ma L; Department of Endocrinology, Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, the First Affiliated Hospital of Chongqing Medical University, China (L.M.)., Shi N; Department of Urology, Northern Jiangsu People's Hospital, China (N.S.)., Zhang Y; Clinical Pharmacology Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, China (Y.Z.)., Sun S; National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, China (S.S.)., Tao J; Department of Urology (J.T.), The First Affiliated Hospital With Nanjing Medical University, China., Bao M; Department of Pathology (M.B.), The First Affiliated Hospital With Nanjing Medical University, China., Zhou M; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China., Wang C; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China., Yang T; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China., Zhang Z; Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China (Z.Z.)., Yang Y; Department of Endocrinology (M.S., M.G., Y.L., Z.X., M.Z., C.W., T.Y., Y.Y.), The First Affiliated Hospital With Nanjing Medical University, China. |
| Πηγή: | Hypertension (Dallas, Tex. : 1979) [Hypertension] 2026 Aug; Vol. 83 (8), pp. e26528. Date of Electronic Publication: 2026 Jun 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE |
| Imprint Name(s): | Publication: Original Publication: [Dallas, Tex.] : [American Heart Association], [©1979]- |
| Ιατρικοί όροι (MeSH): | Aldosterone*/biosynthesis , Aldosterone*/metabolism , Propionates*/metabolism , Adrenal Cortex Neoplasms*/metabolism , Adrenal Cortex Neoplasms*/genetics , Adrenal Cortex Neoplasms*/pathology , Adenoma*/metabolism , Adenoma*/pathology , Adenoma*/genetics, Adrenal Cortex/metabolism ; Cytochrome P-450 CYP11B2/metabolism ; Cytochrome P-450 CYP11B2/genetics ; Reactive Oxygen Species/metabolism ; Calcium Channels, L-Type/metabolism ; Hyperaldosteronism/metabolism ; Animals ; Mice ; Humans ; Oxidation-Reduction ; Female ; Metabolic Reprogramming ; Oxidative Stress |
| Περίληψη: | Background: Metabolic reprogramming is increasingly recognized as a key driver of endocrine tumor biology, yet how dysregulated metabolism promotes aldosterone excess in aldosterone-producing adenomas remains largely unclear. Methods: Multiomics profiling of human adrenal and blood specimens was performed to identify metabolic reprogramming. Dysregulated genes and accumulation of intermediates in the propionate metabolism were validated in aldosterone-producing adenomas. Functional effects on aldosterone production were assessed in adrenocortical cells and mice. Key downstream molecules and pathways were examined through transcriptomics, mass spectrometry, and targeted functional assays. Results: Aldosterone-producing adenomas exhibited reprogrammed propionate metabolism and accumulation of its byproduct methylmalonic acid, associated with upregulation of the upstream enzyme PCCA (propionyl-CoA carboxylase subunit A). In adrenocortical cells, PCCA overexpression increased CYP11B2 (aldosterone synthase) expression and aldosterone production, while its silencing had the opposite effects. In both adrenocortical cells and female mouse adrenals, methylmalonic acid promoted CYP11B2 expression and aldosterone production. Mechanistically, methylmalonic acid elevated reactive oxygen species, which triggered S-glutathionylation modification of the L-type calcium channel Ca Conclusions: These findings identify a methylmalonic acid-oxidative stress-Ca |
| Competing Interests: | None. |
| Contributed Indexing: | Keywords: adrenal glands; calcium; calmodulin; methylmalonic acid; oxidative stress |
| Substance Nomenclature: | 4964P6T9RB (Aldosterone) 0 (Propionates) EC 1.14.15.4 (Cytochrome P-450 CYP11B2) 0 (Reactive Oxygen Species) 0 (Calcium Channels, L-Type) |
| Entry Date(s): | Date Created: 20260604 Date Completed: 20260715 Latest Revision: 20260715 |
| Update Code: | 20260716 |
| DOI: | 10.1161/HYPERTENSIONAHA.125.26528 |
| PMID: | 42237910 |
| Βάση Δεδομένων: | MEDLINE |
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