Effect of phosphodiesterase type 4 on circadian clock gene Per1 transcription.
The induction of Per1 gene in the suprachiasmatic nucleus, the center of the circadian clock, is assumed to play significant roles in the adjustment of the internal clock. cAMP is one of the intracellular mediators which activates Per1 transcription. Here, we showed that the amount of the rat Per1 (rPer1) transcript induced by forskolin (FK) was significantly upregulated by the inhibition of phosphodiesterase type 4 (PDE4), a specific phosphodiesterase for cAMP, in rat-1 fibroblasts. Administration of rolipram, a specific inhibitor of PDE4, increased intracellular cAMP concentration, phosphorylation of cAMP response element binding protein (CREB) and enhanced rPer1 induction at their peaks. However, in the falling phase of rPer1 induction, the inhibition of PDE4 hardly affected the profile of rPer1 expression. These findings suggest the involvement of PDE4 for the regulation of rPer1 expression via cAMP metabolism at peak of the induction but little or no participation of PDE4 in the decreasing phase of the gene expression.
Masumoto
Koh-hei
KH
Department of Physics, Informatics and Biology, Yamaguchi University, Yoshida, 753-8512, Yamaguchi, Japan.
Fujioka
Atsuko
A
Nakahama
Ken-ichi
K
Inouye
Shin-Ichi T
ST
Shigeyoshi
Yasufumi
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D005576:Colforsin / Q000378:metabolism; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D056950:Period Circadian Proteins; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D051381:Rats; D020889:Rolipram / Q000378:metabolism; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D009687:Nuclear Proteins; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram