title: Gq/11-induced intracellular calcium mobilization mediates Per2 acute induction in Rat-1 fibroblasts.
abstract: Phase resetting is one of the essential properties of circadian clocks that is required for the adjustment to a particular environment and the induction of Per1 and Per2 clock genes is believed to be a primary molecular event during this process. Although the intracellular signal transduction pathway underlying Per1 gene activation has been well characterized, the mechanisms that control Per2 up-regulation have not yet been elucidated. In our present study, we demonstrate that Gq/11 coupled receptors mediate serum-induced immediate rat Per2 (rPer2) transactivation in Rat-1 fibroblasts via intracellular Ca2+ mobilization. Stimulation of these cells with a high concentration of serum was found to rapidly increase the intracellular Ca2+ levels and strongly up-regulated rPer2 gene. rPer2 induction by serum stimulation was abrogated by intracellular Ca2+ chelation and depletion of intracellular Ca2+ store, which suggests that the calcium mobilization is necessary for the up-regulation of rPer2 gene. In addition, suppression of Gq/11 function was observed to inhibit both Ca2+ mobilization and rPer2 induction. Further, we demonstrated that endothelin-induced acute rPer2 transactivation via Gq/11-coupled endothelin receptors is also suppressed by a Gq/11 specific inhibitor. These findings together suggest that serum and endothelin utilize a common Gq/11-PLC mediated pathway for the transactivation of rPer2, which involves the mobilization of calcium from the intracellular calcium store.
authors.affiliation: Department of Anatomy and Neurobiology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takashima
authors.forename: Atsuko
authors.initials: A
authors.lastname: Fujioka
authors.forename: Naoto
authors.initials: N
authors.lastname: Hayasaka
authors.forename: Ayako
authors.initials: A
authors.lastname: Matsuo
authors.forename: Jun
authors.initials: J
authors.lastname: Takasaki
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Shigeyoshi
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008954:Models, Biological; D009570:Nitriles / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics*; D010456:Peptides, Cyclic / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors
chemical_list: D002070:Butadienes; D009570:Nitriles; D009687:Nuclear Proteins; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D014157:Transcription Factors; C113580:U 0126; C475455:YM-254890; D004533:Egtazic Acid; D015759:Ionomycin; D019284:Thapsigargin; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020741:rho GTP-Binding Proteins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid