BMAL1 in the Adrenal Gland: It's About Time-A Perspective on "Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior".
BMAL1 in the Adrenal Gland: It's About Time-A Perspective on "Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior".
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DOI：
10.1093/function/zqad008
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发表时间：
2023
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生物钟总是在滴答作响，努力使我们的行为和内部生理与外部世界的节奏同步。在哺乳动物中，昼夜节律钟可以分为两个系统：位于下丘脑交叉上核的核心时钟和周围时钟，它们是细胞自主的，几乎在每个组织中运作。[1]这两个系统都调节生物过程，并依赖于被称为时间表的信号来进行夹带。2在分子水平上，生物钟由核心蛋白质组成，这些蛋白质在反馈回路中共同作用以调节昼夜节律。1该环的正臂由异二聚体BMAL 1：CLOCK组成，其激活Per和Cry基因的转录。3负臂包含正调控环的蛋白产物CRY和PER，其抑制BMAL 1和CLOCK活性，从而抑制其自身的转录。生物钟基因的突变会扰乱睡眠行为并导致疾病。3血压表现出强烈的昼夜节律，包括休息期间的“下降”和清醒时的激增;这种模式的丧失与心血管疾病有关。值得注意的是，PER 1、4 β 1/β 2、5和BMAL 1 6的全动物敲除（KO）动物显示血压表型。近年来，外周生物钟在血压调节中也起着重要作用。当在平滑肌、血管周围脂肪和各种组织中的时钟基因缺失时，血压和/或血管功能就会发生改变。
The circadian clock is always ticking, working to synchronize both our behaviors and our internal physiology to the rhythms of the outside world. In mammals, the circadian clock can be divided into two systems: the core clock, located in the hypothalamic superchiasmatic nucleus, and the peripheral clocks, which are cell autonomous and operate in nearly every tissue. 1 Both systems regulate biological processes, and rely on cues known as zeitgebers for entrainment. 2 On a molecular level, the biological clock consists of core proteins that work together in a feedback loop to regulate the circadian rhythm. 1 The positive arm of this loop consists of the heterodimer, BMAL1: CLOCK, which activates transcription of Per and Cry genes. 3 The negative arm comprises the protein products of the positive regulatory loop, CRY and PER, which repress BMAL1 and CLOCK activity, and thus suppress their own transcription. 3 Mutations in clock genes can disrupt sleeping behaviors and contribute to disease. 3Blood pressure exhibits a strong circadian rhythm, including a “dip” during the resting period and a surge upon waking; loss of this pattern is associated with cardiovascular disease. Of note, whole animal knockout (KO) animals for PER1, 4 CRY1/CRY2, 5 and BMAL1 6 display blood pressure phenotypes. In recent years, it has become apparent that the peripheral circadian clocks also play a role in blood pressure regulation. Altered blood pressure and/or vascular function occurs when clock genes are deleted in smooth muscle, perivascular adipose, and various