{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:26:20Z","timestamp":1756189580993},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["2015R1D1A1A01056668","2015K1A3A7A08074157"],"award-info":[{"award-number":["2015R1D1A1A01056668","2015K1A3A7A08074157"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HI13C1527"],"award-info":[{"award-number":["HI13C1527"]}],"id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Summary<\/jats:title>A mutation in the mineralocorticoid receptor (MRS<\/jats:sub><\/jats:styled-content>810L<\/jats:sub>) leads to early\u2010onset hypertension, which is markedly exacerbated during pregnancy. The mutation causes progesterone and even the MR<\/jats:styled-content> antagonist spironolactone to become potent agonists. Thus, it is hard to control hypertension in patients harbouring this mutation. We hypothesized that histone deacetylase inhibition (HDAC<\/jats:styled-content>i), but not the MR<\/jats:styled-content> antagonist spironolactone, attenuates atypical transcriptional activity of activating mutant MR<\/jats:styled-content> (MRS<\/jats:sub><\/jats:styled-content>810L<\/jats:sub>). We established HEK<\/jats:styled-content>293T cells overexpressing wild\u2010type MR<\/jats:styled-content> (MRWT<\/jats:sub><\/jats:styled-content>) or MRS<\/jats:sub><\/jats:styled-content>810L<\/jats:sub> and determined their transcriptional activities by luciferase assay. Expression of MR<\/jats:styled-content> target genes was measured by quantitative real\u2010time PCR<\/jats:styled-content> (qRT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>). Treatment with aldosterone increased the expression of MR<\/jats:styled-content> target genes as well as the transcriptional activities in HEK<\/jats:styled-content>293T cells transfected either with MRWT<\/jats:sub><\/jats:styled-content> or MRS<\/jats:sub><\/jats:styled-content>810L<\/jats:sub>. Treatment with either spironolactone or progesterone also increased the expression of MR<\/jats:styled-content> target genes as well as transcriptional activity, but only in HEK<\/jats:styled-content>293T cells transfected with MRS<\/jats:sub><\/jats:styled-content>810L<\/jats:sub>. Spironolactone abolished the promoter activity stimulated by aldosterone in HEK<\/jats:styled-content>293T cells transfected with MRWT<\/jats:sub><\/jats:styled-content>. Treatment with HDAC<\/jats:styled-content> inhibitors attenuated the transcriptional activity as well as the expression of MR<\/jats:styled-content> target genes induced by aldosterone, spironolactone, or progesterone whether HEK<\/jats:styled-content>293T cells were transfected with either MRWT<\/jats:sub><\/jats:styled-content> or MRS<\/jats:sub><\/jats:styled-content>810L<\/jats:sub>. These results indicate that HDAC<\/jats:styled-content>i, but not an MR<\/jats:styled-content> antagonist spironolactone, attenuates atypical transcriptional activity of an activating mutant MR<\/jats:styled-content> (MRS<\/jats:sub><\/jats:styled-content>810L<\/jats:sub>).<\/jats:p>","DOI":"10.1111\/1440-1681.12614","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T17:40:39Z","timestamp":1467308439000},"page":"995-1003","source":"Crossref","is-referenced-by-count":3,"title":["Histone deacetylase inhibition, but not a mineralocorticoid receptor antagonist spironolactone, attenuates atypical transcription by an activating mutant MR<\/scp> (MRS<\/sub><\/scp>810L<\/sub>)"],"prefix":"10.1111","volume":"43","author":[{"given":"Seol\u2010Hee","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Pharmacology Cardiovascular Research Institute Cell and Matrix Research Institute Kyungpook National University School of Medicine Daegu 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