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http://purl.uniprot.org/citations/24285684http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24285684http://www.w3.org/2000/01/rdf-schema#comment"

Context

The molecular mechanisms of primary aldosteronism, a common cause of human hypertension, are unknown, but alterations of K(+) channels can play a key role.

Objective

The objective of the study was to investigate the following: 1) the expression of the Twik-related acid-sensitive K(+) channels (TASK) in aldosterone producing adenomas (APAs); 2) the role of TASK-2 in aldosterone synthesis; and 3) the determinants of TASK-2-blunted expression in APAs.

Design

We analyzed the transcriptome and the microRNA profiles of 32 consecutive APAs and investigated the protein expression and localization of TASK-2 in APA and adrenocortical cell lines (H295R and HAC15) using immunoblotting and confocal microscopy. The functional effect of TASK-2 blunted activity caused by a dominant-negative mutation on steroidogenic enzymes, and aldosterone production was also assessed. TASK-2 regulation by selected microRNA was studied by a luciferase assay.

Results

TASK-2 was consistently less expressed at the transcript and protein levels in APAs than in the normal human adrenal cortex. H295R cell transfection with a TASK-2 dominant-negative mutant construct significantly increased the aldosterone production by 153% and the gene expression of aldosterone synthase (CYP11B2, gene expression fold change 3.1 vs control, P < .05) and the steroidogenic acute regulatory protein (gene expression fold change 1.8 vs control, P < .05). Two microRNAs, hsa-miR-23 and hsa-miR-34, were found to decrease the TASK-2 expression by binding to the 3' untranslated region of the TASK-2 gene.

Conclusions

The TASK-2 channel lower expression represents a hallmark of APA and is associated with a higher expression of hsa-miR-23 and hsa-miR-34. The ensuing blunted TASK-2 activity increased the production of aldosterone in vitro and the expression of steroidogenic acute regulatory protein and CYP11B2. Hence, the lower expression of TASK-2 channel in APA cells can explain high aldosterone secretion in human primary aldosteronism despite the suppression of angiotensin II, hypertension, and hypokalemia."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.org/dc/terms/identifier"doi:10.1210/jc.2013-2900"xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Bader M."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Rainey W.E."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Belloni A.S."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Lenzini L."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Rossi G.P."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Seccia T.M."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Skander G."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Ferraro S."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Fassina A."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Caroccia B."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Kuppusamy M."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/author"Campos A.G."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/pages"E674-82"xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/title"Lower expression of the TWIK-related acid-sensitive K+ channel 2 (TASK-2) gene is a hallmark of aldosterone-producing adenoma causing human primary aldosteronism."xsd:string
http://purl.uniprot.org/citations/24285684http://purl.uniprot.org/core/volume"99"xsd:string
http://purl.uniprot.org/citations/24285684http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24285684
http://purl.uniprot.org/citations/24285684http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24285684
http://purl.uniprot.org/uniprot/#_A0A0B6VPR3-mappedCitation-24285684http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24285684
http://purl.uniprot.org/uniprot/#_O95279-mappedCitation-24285684http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24285684
http://purl.uniprot.org/uniprot/A0A0B6VPR3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/24285684
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