Akademik Veri Yönetim Sistemi
TRYPTOPHAN METABOLISM: IMPLICATIONS FOR BIOLOGICAL PROCESSES, HEALTH AND DISEASE, ss.269-289, 2015 (SCI-Expanded)
In mammals, melatonin is synthesized not only in the pineal gland but also in many other parts of the body. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the central suprachiasmatic nucleus (SCN) clock. This circadian pacemaker encodes rhythmic output in accordance with light input. Environmental light is sensed by an intrinsically photosensitive retinal ganglion cells (ipRGCs). Circadian rhythmicity in the SCN originates from the interaction of a defined set of "clock genes." Melatonin is able to alter the levels of various circadian rhythm genes by re-synchronizing a rhythmic pattern of clock gene expression. Silent mating type information regulation 2 homolog-1 (Sirt1), a nicotinamide adenine dinucleotide [NAD(+)]-dependent histone deacetylase, is required for circadian clock gene expression. Altered circadian rhythm regulation plays a critical role in carcinogenesis. Melatonin significantly inhibits Sirt1 protein transcription and activity in multiple human cancer cell lines. However, light is able to either suppress or synchronize melatonin production according to the light schedule. Therefore in industrialized countries, night-shift workers are at high risk for circadian disruption. Epidemiological studies displayed that the increase in breast cancer risk in night-shift workers is associated with exposure to light at night. Furthermore age-related changes reflect a decline in pacemaker amplitude, due to alteration of SCN functions and systems under its control. Consequently dysfunction of endogenous clocks, melatonin receptor polymorphisms, and age-associated decline of melatonin synthesis are already increased risks of breast cancer.