title: Resetting of peripheral circadian clock by prostaglandin E2.
abstract: In mammals, the master circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is thought to drive peripheral oscillators by controlling neuronal and humoral signals that can entrain the peripheral clocks. Here, we show that prostaglandin E2 (PGE2), a proinflammatory compound known to have diverse biological effects, is able to act as an in vivo clock-resetting agent. We find that in cultured NIH3T3 fibroblasts, PGE2 is able to induce transient expression of Period 1 messenger RNA and the following circadian oscillation of clock gene expression. Furthermore, we demonstrate that intraperitoneal administration of PGE2 results in the phase shift of circadian gene expression in mouse peripheral tissues in a time-dependent manner. This phase shift is also induced by the EP1/EP3 agonist sulprostone but not by the EP2 agonist butaprost. The PGE2-induced phase shift is inhibited by the EP1 antagonist SC-51322. These results suggest that PGE2 acts as an in vivo clock-resetting factor by means of the EP1 subtype of PGE receptors.
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: Itsunari
authors.initials: I
authors.lastname: Minami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kadotani
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects* / Q000502:physiology*; D018797:Cell Cycle Proteins; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; C545636:Ptger1 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone
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