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内容記述 |
In mammalian central clock neurons of the suprachiasmatic nucleus (SCN), cAMP signaling is rhythmically activated by extracellular neuropeptides for amplification of intracellular oscillations. Recent studies revealed that Ca2+, another clock-input signaling, is incorporated into a cell-autonomous oscillation mechanism in various organisms. The study provided a chance for reconsideration of the self-sustained oscillation mechanism of the circadian clock. The present study investigated whether cAMP signaling was involved in the autonomous oscillation of cultured cells. Here, we show that the SCN neurons show clear circadian cAMP rhythms that are sensitive to an adenylyl cyclase inhibitor, MDL-12,330A. On the other hand, no apparent circadian rhythm of cAMP was observed in Rat-1 fibroblasts. Consistently, MDL-12,330A showed no significant effects on circadian oscillation of Per1, Per2, Bmal1 and D-box-dependent transcription. Similarly, no obvious effects of MDL-12,330A on rhythmic gene expression of Per2 and Bmal1 were observed in human U2OS cells. These results showed no significant role of cAMP signaling for cell-autonomous oscillations in cultured cells. In contrast, extracellular activation of cAMP signaling by forskolin caused a phase-shift of transcriptional rhythms of Per2 in Rat-1 fibroblasts. These results indicate that cAMP signaling is specifically involved in the clock input pathway from extracellular signals. |
