Review Article Clockworks in the Central and Peripheral Organs: from Clock-related Genes to the Physiological and Pathological Rhythms

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Abstract

Daily rhythms such as sleep-wake, feeding, and the core body temperature, persist with a period of approximately 24 hr even in the absence of environmental time cues, suggesting the existence of an endogenous time-keeping system, the circadian clock. In mammals, the circadian clock is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Recently, a number of studies have revealed that circadian oscillations in the SCN are driven by the intracellular transcriptional and post-translational negative feedback loop formed by several clock-related genes such as Period (Per) and clock genes. Surprisingly, this feedback loop was found in many peripheral organs, indicating that the physiological and pathological rhythms in the peripheral organs were generated by the local clock in the peripheral organs, which synchronize to the central clock in the SCN. In addition several humoral factors seem to medi- aa, ate communication between the central and peripheral clocks. Furthermore, the transcription of some genes encoding the disease risk factors were found to be directly regulated by the clock genes, suggesting the possible involvement of clock genes in the onset of some diseases. In this article, we review the current view on the molecular mechanism underlying circadian oscillations in the central clock within the SCN and the local clock in the peripheral and discuss the relationship between clock genes, and physiological and pathological rhythm.

Acta medica Nagasakiensia. 2003, 48(1-2), p.1-7

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