Selective upregulation of Per1 mRNA expression by ATP through activation of P2X7 purinergic receptors expressed in microglial cells

Ryota Nakazato, Takeshi Takarada, Tomomi Yamamoto, Shogo Hotta, Eiichi Hinoi, Yukio Yoneda

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)350-361
Number of pages12
JournalJournal of Pharmacological Sciences
Volume116
Issue number4
DOIs
Publication statusPublished - 2011
Externally publishedYes

Fingerprint

Purinergic P2X7 Receptors
Up-Regulation
Adenosine Triphosphate
Messenger RNA
Microglia
Luciferases
Purinergic P2X Receptor Antagonists
Period Circadian Proteins
Genes
Suprachiasmatic Nucleus
Circadian Rhythm
Small Interfering RNA
Transcriptional Activation
Plasmids
Cell Count
Fluorescence
Gene Expression
Cell Line
Brain

Keywords

  • ATP
  • Clock gene
  • Microglia
  • P2X7 subtype

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Selective upregulation of Per1 mRNA expression by ATP through activation of P2X7 purinergic receptors expressed in microglial cells. / Nakazato, Ryota; Takarada, Takeshi; Yamamoto, Tomomi; Hotta, Shogo; Hinoi, Eiichi; Yoneda, Yukio.

In: Journal of Pharmacological Sciences, Vol. 116, No. 4, 2011, p. 350-361.

Research output: Contribution to journalArticle

Nakazato, Ryota ; Takarada, Takeshi ; Yamamoto, Tomomi ; Hotta, Shogo ; Hinoi, Eiichi ; Yoneda, Yukio. / Selective upregulation of Per1 mRNA expression by ATP through activation of P2X7 purinergic receptors expressed in microglial cells. In: Journal of Pharmacological Sciences. 2011 ; Vol. 116, No. 4. pp. 350-361.
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