title: Selective upregulation of Per1 mRNA expression by ATP through activation of P2X7 purinergic receptors expressed in microglial cells.
abstract: Clock genes are believed to play a pivotal role in the generation and oscillation of circadian rhythm as a central clock in the hypothalamic suprachiasmatic nucleus in the mammalian brain. In this study, mRNA expression was for the first time demonstrated with clock genes in both cultured murine microglia and microglial cell line BV-2 cells. Exposure to ATP transiently increased Period-1 (Per1) mRNA expression without affecting that of other clock genes in BV-2 cells, while a similarly transient increase was shown in Per1 mRNA expression in a manner sensitive to P2X7 purinergic receptor antagonists in cultured microglia exposed to ATP. In BV-2 cells transfected with a Per1 promoter luciferase reporter plasmid, ATP significantly increased luciferase activity in a manner sensitive to a P2X7-receptor antagonist. In both microglia and BV-2 cells, a significant increase by ATP was seen in the immunocytochemical fluorescence intensity of cells expressing Per1 protein, with mRNA expression of different P2 receptors including P2X7. Per1 siRNA significantly decreased the number of cells with processes in BV-2 cells exposed to ATP. These results suggest that ATP selectively promotes Per1 expression through gene transactivation after stimulation of P2X7 purinergic receptors in microglial cells.
authors: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Japan.
authors: Ryota
authors: R
authors: Nakazato
authors: Takeshi
authors: T
authors: Takarada
authors: Tomomi
authors: T
authors: Yamamoto
authors: Shogo
authors: S
authors: Hotta
authors: Eiichi
authors: E
authors: Hinoi
authors: Yukio
authors: Y
authors: Yoneda
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D058920:Purinergic P2X Receptor Antagonists; D012333:RNA, Messenger; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D008156:Luciferases