Aldosterone induces circadian gene expression of clock genes in H9c2 cardiomyoblasts.
We examined mRNA expression of the clock genes (Per1, Per2, and Bmal1) and PAI-1 (plasminogen activator inhibitor-1) after aldosterone treatment every 4 h up to 48 h in H9c2 cardiomyoblasts by reverse transcription-polymerase chain reaction. To block the MR (mineralocorticoid receptor), the MR antagonist, spironolactone, was added to the medium 1 h before aldosterone treatment. Aldosterone induced an initial increase and rhythmic expression of Per1, while spironolactone attenuated the acute increase in Per1 mRNA induced by aldosterone. On the other hand, aldosterone did not increase the Per2 mRNA in the acute phase, but thereafter induced a rhythmic expression of Per2. Aldosterone also induced rhythmic expression of Bmal1, a positive element of the clock genes. The rhythm of Bmal1 mRNA was anti-phase of that of Per2 mRNA. Aldosterone induced an acute increase in PAI-1 mRNA, but did not induce rhythmic expression of PAI-1. The present study demonstrated first that aldosterone regulates expression of the clock genes Per1, Per2, and Bmal1, and increases PAI-1 expression in H9c2 cardiomyoblasts. Second, an acute increase in Per1 mRNA after aldosterone treatment is mediated through MR. Third, clock genes are not related to PAI-1 expression in H9c2 cardiomyoblasts.
Tanaka
Kyoe
K
Division of Cardiovascular Medicine, Department of Translational Medical Sciences, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. kyoe@net.nagasaki-u.ac.jp
Ashizawa
Naoto
N
Kawano
Hiroaki
H
Sato
Osami
O
Seto
Shinji
S
Nishihara
Eijun
E
Terazono
Hideyuki
H
Isomoto
Shojiro
S
Shinohara
Kazuyuki
K
Yano
Katsusuke
K
D056930:ARNTL Transcription Factors; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*
D056930:ARNTL Transcription Factors; D000450:Aldosterone; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D015534:Trans-Activators; C539024:Per1 protein, rat; C513311:Per2 protein, rat; C538945:Clock protein, rat