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 spermi-dine—a polyamine—strongly induced circadian phase advances in the presence or absence of dexamethasone (a synthetic glucocorticoid) in NIH3T3 cells transfected with the Bmal1 promo-tor-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 glucocorti-coid 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 sug-gested 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 desyn-chrony.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)