Aldosterone induces circadian gene expression of clock genes in H9c2 cardiomyoblasts

Abstract

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.

Molecular basis of circadian rhythmicity in renal physiology and pathophysiology

“…Cortisol has been proposed as a synchronizing signal yet adrenalectomized animals still exhibit strong circadian fluctuations in physiological function (Moore-Ede, 1986). Our identification of Per1 as an aldosterone target gene has been validated by the findings of several other groups that aldosterone induces Per1 expression in the kidney and cardiomyoblasts (Tanaka et al , 2007; Le Billan et al , 2015). Per1 appears to be unique among the clock genes in being induced by aldosterone and cortisol.…”

The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice

“…Microarray analysis in a human adrenocortical cell line after angiotensin II treatment demonstrated that Per1 was upregulated 3-fold compared with control (24). Per1 and Per2 were induced by aldosterone in cardiomyoblasts, an effect that was blocked by spironolactone (32). Another connection between hormone signaling and Per1 was demonstrated by Balsalobre et al They found that glucocorticoids reset circadian timing in peripheral tissues, including the kidney, by inducing the expression of Per1 (33).…”

Arterial Hypertension, Atrial Fibrillation, and Hyperaldosteronism

“…52 The deposition of fibrotic tissue, by decreasing gap junctions coupling and creating muscle bundle discontinuities, alters the spatial location and propagation of depolarization waves, thereby reducing conduction velocity and promoting re-entry circuits. 52,53 Because of the relatively low membrane potential of fibroblasts (-30 mV), fibroblast-cardiomyocyte coupling promotes delayed after-depolarization of the cardiomyocytes and ectopic firing. 52 It also increases transient Ca 2+ amplitude, leading to increased intracellular Ca 2+ concentrations and spontaneous sarcoplasmic reticulum Ca 2+ release, finally favoring AF maintenance 52 (Figure S1).…”