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Title: Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6.
Authors: Doi, Masao  kyouindb  KAKEN_id
Takahashi, Yukari
Komatsu, Rie
Yamazaki, Fumiyoshi
Yamada, Hiroyuki
Haraguchi, Shogo
Emoto, Noriaki
Okuno, Yasushi  kyouindb  KAKEN_id
Tsujimoto, Gozoh
Kanematsu, Akihiro
Ogawa, Osamu  kyouindb  KAKEN_id
Todo, Takeshi
Tsutsui, Kazuyoshi
van der Horst, Gijsbertus T J
Okamura, Hitoshi
Author's alias: 岡村, 均
土居, 雅夫
Issue Date: Jan-2010
Publisher: Nature Publishing Group
Journal title: Nature medicine
Volume: 16
Issue: 1
Start page: 67
End page: 74
Abstract: Malfunction of the circadian clock has been linked to the pathogenesis of a variety of diseases. We show that mice lacking the core clock components Cryptochrome-1 (Cry1) and Cryptochrome-2 (Cry2) (Cry-null mice) show salt-sensitive hypertension due to abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal gland. An extensive search for the underlying cause led us to identify type VI 3beta-hydroxyl-steroid dehydrogenase (Hsd3b6) as a new hypertension risk factor in mice. Hsd3b6 is expressed exclusively in aldosterone-producing cells and is under transcriptional control of the circadian clock. In Cry-null mice, Hsd3b6 messenger RNA and protein levels are constitutively high, leading to a marked increase in 3beta-hydroxysteroid dehydrogenase-isomerase (3beta-HSD) enzymatic activity and, as a consequence, enhanced aldosterone production. These data place Hsd3b6 in a pivotal position through which circadian clock malfunction is coupled to the development of hypertension. Translation of these findings to humans will require clinical examination of human HSD3B1 gene, which we found to be functionally similar to mouse Hsd3b6.
Description: 生体リズム異常に伴う高血圧発症メカニズムを解明しました. 京都大学プレスリリース. 2009-12-14.
Rights: c 2010 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 許諾条件により本文は2010-07-01に公開.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
DOI(Published Version): 10.1038/nm.2061
PubMed ID: 20023637
Appears in Collections:Journal Articles

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