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Proteomic Landscape of Aldosterone-Producing Adenoma

Swierczynska, Marta M. and Betz, Matthias J. and Colombi, Marco and Dazert, Eva and Jenö, Paul and Moes, Suzette and Pfaff, Cécile and Glatz, Katharina and Reincke, Martin and Beuschlein, Felix and Donath, Marc Y. and Hall, Michael N.. (2018) Proteomic Landscape of Aldosterone-Producing Adenoma. Hypertension (Dallas, Tex. : 1979), 73 (2). pp. 469-480.

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Official URL: https://edoc.unibas.ch/68039/

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Abstract

Primary aldosteronism is a disease of excessive production of adrenal steroid hormones and the most common cause of endocrine hypertension. Primary aldosteronism results mainly from bilateral adrenal hyperplasia or unilateral aldosterone-producing adenoma (APA). Primary aldosteronism cause at the molecular level is incompletely understood and a targeted treatment preventing excessive adrenal steroid production is not available. Here, we perform deep quantitative proteomic and phosphoproteomic profiling of 6 pairs of APA and adjacent nontumoral adrenal cortex. We show that increased steroidogenesis in APA is accompanied by upregulation of steroidogenic enzymes (HSD3B2, CYP21A2, CYP11B2) and of proteins involved in cholesterol uptake (LSR). We demonstrate that HSD3B2 is phosphorylated at Ser95 or 96 and identify a novel phosphorylation site, Ser489, in CYP21A2, suggesting that steroidogenic enzymes are regulated by phosphorylation. Our analysis also reveals altered ECM (extracellular matrix) composition in APA that affects ECM-cell surface interactions and actin cytoskeleton rearrangements. We show that RHOC, a GTPase controlling actin organization in response to extracellular stimuli, is upregulated in APA and promotes expression of the aldosterone synthase gene CYP11B2. Our data also indicate deregulation of protein N-glycosylation and GABAergic signaling in APAs. Finally, we find that mTORC1 (mammalian target of rapamycin complex 1) signaling is the major pathway deregulated in APA. Our study provides a rich resource for future research on the molecular mechanisms of primary aldosteronism.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1524-4563
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:16 Apr 2020 12:56
Deposited On:16 Apr 2020 12:56

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