{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:54:14Z","timestamp":1790816054058,"version":"4.1.0"},"reference-count":50,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>\n                    Somatic and germline mutations in the inward-rectifying K\n                    <jats:sup>+<\/jats:sup>\n                    channel (\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    ) are a common cause of primary aldosteronism (PA) in aldosterone-producing adenoma and familial hyperaldosteronism type III, respectively. Dysregulation of adrenal cell calcium signaling represents one mechanism for mutated\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    stimulation of aldosterone synthase (\n                    <jats:italic>CYP11B2<\/jats:italic>\n                    ) expression and aldosterone production. However, the mechanisms stimulating acute and chronic production of aldosterone by mutant\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    have not been fully characterized. Herein, we defined the effects of the T158A\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    mutation (\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    ) on acute and chronic regulation of aldosterone production using an adrenal cell line with a doxycycline-inducible\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    gene (HAC15-TRE-\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    ). Doxycycline incubation caused a time-dependent increase in\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>CYP11B2<\/jats:italic>\n                    mRNA and protein levels. Electrophysiological analyses confirm the loss of inward rectification and increased Na\n                    <jats:sup>+<\/jats:sup>\n                    permeability in\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    -expressing cells.\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    expression also led to the activation of\n                    <jats:italic>CYP11B2<\/jats:italic>\n                    transcriptional regulators, NURR1 and ATF2. Acutely,\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    stimulated the expression of total and phosphorylated steroidogenic acute regulatory protein (StAR).\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    expression increased the synthesis of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol, measured with liquid chromatography-tandem mass spectrometry (LC-MS\/MS). All of these stimulatory effects of\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    were inhibited by the L-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel blocker, verapamil. Overall,\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    increases\n                    <jats:italic>CYP11B2<\/jats:italic>\n                    expression and production of aldosterone, corticosterone and hybrid steroids by upregulating both acute and chronic regulatory events in aldosterone production, and verapamil blocks\n                    <jats:italic>\n                      KCNJ5\n                      <jats:sup>T158A<\/jats:sup>\n                    <\/jats:italic>\n                    -mediated pathways leading to aldosterone production.\n                  <\/jats:p>","DOI":"10.1530\/jme-15-0324","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T01:33:54Z","timestamp":1461202434000},"page":"1-11","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":40,"title":["Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production"],"prefix":"10.1530","volume":"57","author":[{"given":"Namita G","family":"Hattangady","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehiro","family":"Karashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ponce-Balbuena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Jalife","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso E","family":"Gomez-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Auchus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E","family":"Rainey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Else","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2016062919131286000_57.1.1.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041926"},{"key":"2016062919131286000_57.1.1.2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-15-0321"},{"key":"2016062919131286000_57.1.1.3","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1016\/S0021-9258(18)94186-4","article-title":"Mitochondrial localization of a phosphoprotein that rapidly accumulates in adrenal cortex cells exposed to adrenocorticotropic hormone or to cAMP","volume":"264","author":"Alberta","year":"1989","journal-title":"Journal of Biological Chemistry"},{"key":"2016062919131286000_57.1.1.4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2965"},{"key":"2016062919131286000_57.1.1.5","doi-asserted-by":"publisher","DOI":"10.3109\/07435800009048620"},{"key":"2016062919131286000_57.1.1.6","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0005"},{"key":"2016062919131286000_57.1.1.7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405431200"},{"key":"2016062919131286000_57.1.1.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(00)00411-1"},{"key":"2016062919131286000_57.1.1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.01.018"},{"key":"2016062919131286000_57.1.1.10","doi-asserted-by":"crossref","unstructured":"Campeau E Ruhl VE Rodier F Smith CL Rahmberg BL Fuss JO Campisi J Yaswen P Cooper PK Kaufman PD 2009 A versatile viral system for expression and depletion of proteins in mammalian cells. 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