National Institute of Advanced Industrial Science and Technology (AIST)
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AIST TODAYNo.42 2011-4 [ PDF:5.1MB ]


Harmine, a new candidate for sleep disorder treatment
- A circadian modulator which extends the circadian period -

[ PDF:800KB ]

We established an assay system using NIH3T3 cells stably expressing a Bmal1 promoter-driven luciferase reporter gene and used the system to analyze circadian oscillation of the gene. We examined the effects of a Hoasca alkaloid, harmine, which has a wide spectrum of pharmacological actions, on circadian rhythms using the validated assay system. Harmine dose-dependently elongated the circadian period. Furthermore, EMSA and Western blot analysis showed that harmine enhanced the transactivating function of RORα, probably by increasing its nuclear translocation. Exogenous expression of RORα also caused a long period, confirming the phenotype indicated by harmine. These results suggest that harmine extends the circadian period by enhancing RORα function and that harmine is a new candidate that contributes to the control of period length in mammalian cells.

Figure 1   Figure 2
Measurement of the elongating effect of harmine on circadian period
Harmine extends period length.
 
Harmine induces RORα accumulation in nuclei and then the circadian period is extended.

Relational Information
AIST TODAY Vol.11 No.7 p.18 (2011)


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