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[生物钟系统的生理和病理生理作用]

[Physiological and pathophysiological role of the circadian clock system].

作者信息

Halmos Tamás, Suba Ilona

机构信息

Mazsihisz Szeretetkórház Metabolikus Ambulancia Budapest Amerikai út 53-55. 1145.

出版信息

Orv Hetil. 2012 Sep 2;153(35):1370-9. doi: 10.1556/OH.2012.29436.

Abstract

It has been well known for ages that in living organisms the rhythmicity of biological processes is linked to the ~ 24-hour light-dark cycle. However, the exact function of the circadian clock system has been explored only in the past decades. It came to light that the photosensitive primary "master clock" is situated in the suprachiasmatic photosensitive nuclei of the special hypothalamic region, and that it is working according to ~24-hour changes of light and darkness. The master clock sends its messages to the peripheral "slave clocks". In many organs, like pancreatic β-cells, the slave clocks have autonomic functions as well. Two essential components of the clock system are proteins encoded by the CLOCK and BMAL1 genes. CLOCK genes are in interaction with endonuclear receptors such as peroxisoma-proliferator activated receptors and Rev-erb-α, as well as with the hypothalamic-pituitary-adrenal axis, regulating the adaptation to stressors, energy supply, metabolic processes and cardiovascular system. Melatonin, the product of corpus pineale has a significant role in the functions of the clock system. The detailed discovery of the clock system has changed our previous knowledge about the development of many diseases. The most explored fields are hypertension, cardiovascular diseases, metabolic processes, mental disorders, cancers, sleep apnoe and joint disorders. CLOCK genes influence ageing as well. The recognition of the periodicity of biological processes makes the optimal dosing of certain drugs feasible. The more detailed discovery of the interaction of the clock system might further improve treatment and prevention of many disorders.

摘要

长久以来人们都熟知,在生物体中,生物过程的节律性与约24小时的明暗循环相关。然而,昼夜节律时钟系统的确切功能仅在过去几十年才得以探索。人们发现,光敏性初级“主时钟”位于特殊下丘脑区域的视交叉上核,且它根据约24小时的明暗变化运行。主时钟将其信息发送至外周“从时钟”。在许多器官中,如胰腺β细胞,从时钟也具有自主功能。时钟系统的两个重要组成部分是由CLOCK和BMAL1基因编码的蛋白质。CLOCK基因与核内受体相互作用,如过氧化物酶体增殖物激活受体和Rev-erb-α,以及与下丘脑-垂体-肾上腺轴相互作用,调节对应激源的适应、能量供应、代谢过程和心血管系统。松果体产生的褪黑素在时钟系统的功能中具有重要作用。时钟系统的详细发现改变了我们此前对许多疾病发展的认知。研究最多的领域包括高血压、心血管疾病、代谢过程、精神障碍、癌症、睡眠呼吸暂停和关节疾病。CLOCK基因也影响衰老。对生物过程周期性的认识使某些药物的最佳给药成为可能。对时钟系统相互作用的更详细发现可能会进一步改善许多疾病的治疗和预防。

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