HL-1心筋細胞株におけるアドレナリン受容体活性化が概日時計遺伝子振動に及ぼす影響

Circadian rhythms are physiological, biochemical and behavioural processes with a 24-h period molecularly regulated by clock genes. Cardiovascular physiology is subject to circadian variations in heart rate, blood pressure and contractility to optimize its function according to the rest-activity phases. Adrenergic receptors (ARs), activated by endogenous catecholamine hormones, are crucial in the regulation of cardiac functions; however, controllable in vitro models to study the intrinsic cardiomyocyte circadian clock with minimal systemic timing cues remain limited. Here, we use HL-1 cardiomyocyte cell line (HL-1 cells), in which serum shock induces synchronized oscillations of core clock gene transcripts compared with unsynchronized cultures. Different ARs activators onto HL-1 cells were applied under non-synchronized or synchronized conditions and circadian oscillation of representative clock genes was determined. We show that alpha- and beta-AR activation differentially modulates clock gene mesor, amplitude and phase. These findings support HL-1 cells as a convenient in vitro platform to investigate interactions between adrenergic signaling and cardiomyocyte clock gene oscillations.