| 摘要 |
Described methods to identify test compounds that alter circadian rhythms of mammals, and more specifically, methods for determining the ability of a test compound to alter hCKI delta and epsilon phosphorylation of a human Period protein. Also described is a method for determining the ability of a test compound to selectively alter phosphorylation, interaction with, or alternatively degradation, of one or more human Period proteins relative to its ability to alter phosphorylation, interaction with, or alternatively degradation, of a different human Period protein. The top graph provides a pictorial representation of the data presented in the bottom graph. The bottom axis is time in hours; the other axis is the relative real-time mRNA levels of hPER1 Ratl fibroblast or Rat SCN cells as determined by RT-PCR. Two test compounds are represented; the test compound represented by boxes is "C", which is added to the cells at 10 ìM, the second test compound is represented by triangles is S943166, which is added to the cells at 10 ìM. These results show that the test compound, S943166, alters the circadian rhythm of cells by shifting the mRNA oscillation of hPER1, and shorten the circadian rhythm to about 20 hrs.
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