Yang Dan, Oike Hideaki, Furuse Mitsuhiro, Yasuo Shinobu
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University.
Food Research Institute, National Agriculture and Food Research Organization.
Biomed Res. 2021;42(5):221-227. doi: 10.2220/biomedres.42.221.
Irregular light-dark cycles desynchronize the circadian clock via hormonal and neuronal pathways and increase the risk of various diseases. This study demonstrated that a single pulse of spermidine-a polyamine-strongly induced circadian phase advances in the presence or absence of dexamethasone (a synthetic glucocorticoid) in NIH3T3 cells transfected with the Bmal1 promotor-driven luciferase reporter gene. The spermidine-induced phase advances were 2-3 fold greater than were the dexamethasone-induced shifts. The phase resetting effect of spermidine occurred in a dose- and time-dependent manner and was not blocked by RU486, an antagonist of glucocorticoid receptors. Spermidine treatment modulated the expression of clock genes within 60 min, which was sooner than changes in the expression of autophagy-related genes. These findings suggested that spermidine is a potent modulator of the circadian phase, acting through glucocorticoid receptor-independent pathways, and may be useful for treating diseases related to circadian desynchrony.
不规律的明暗周期通过激素和神经通路使生物钟失调，并增加患各种疾病的风险。本研究表明，在转染了Bmal1启动子驱动的荧光素酶报告基因的NIH3T3细胞中，无论是在存在还是不存在地塞米松（一种合成糖皮质激素）的情况下，单脉冲亚精胺（一种多胺）都能强烈诱导昼夜节律相位提前。亚精胺诱导的相位提前比地塞米松诱导的相位变化大2至3倍。亚精胺的相位重置效应呈剂量和时间依赖性，且不受糖皮质激素受体拮抗剂RU486的阻断。亚精胺处理在60分钟内调节了生物钟基因的表达，这比自噬相关基因表达的变化要早。这些发现表明，亚精胺是昼夜节律相位的有效调节剂，通过不依赖糖皮质激素受体的途径发挥作用，可能对治疗与昼夜节律失调相关的疾病有用。
