Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture

Masashi Akiyama, Youichi Minami, Tatsuki Nakajima, Takahiro Moriya, Shigenobu Shibata

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Mammalian circadian clock genes Per1 and Per2 are rhythmically expressed not only in the suprachiasmatic nucleus where the mammalian circadian clock exists, but also in other brain regions and peripheral tissues. The induced circadian oscillation of Per genes after treatment with high concentrations of serum or various drugs in cultured cells suggests the ubiquitous existence of the oscillatory mechanism. These treatments also result in a rapid surge of expression of Per1. It has been shown that multiple signaling pathways are involved in Per1 gene induction in culture cells. We used a dispersed primary cell culture made up of mouse cerebellar granule cells to examine the stimuli inducing the mPer genes and their signaling pathways in neuronal tissues expressing mPer genes. We demonstrated that mPer1, but not mPer2, mRNA expression was dependent on the depolarization state controlled by extracellular KCl concentration in the granule cell culture. Nifedipine treatment reduced mPer1 induction, suggesting that mPer1 mRNA expression depends on intracellular calcium concentration regulated through a voltage-dependent Ca2+ channel. Transient mPer1 mRNA induction was observed after elevating KCl concentration in the medium from 5 mM to 25 mM. This increased expression was suppressed by a calmodulin antagonist, or CaMKII/IV inhibitor, but not by MEK inhibitors. Addition of pituitary adenylate cyclase-activating polypeptide-38 to the medium also induced transient Per1 gene expression. This induction was mimicked by dibutyryl-cAMP and suppressed by a protein kinase A (PKA) inhibitor, but not by MEK inhibitors. These results suggest that Ca2+/calmodulin-dependent protein kinase II/IV- and PKA-dependent pathways are involved in high-KCl and PACAP-induced mPer1 induction, respectively, and neural tissues use multiple signaling pathways for mPer1 induction similar to culture cells.

    Original languageEnglish
    Pages (from-to)499-508
    Number of pages10
    JournalJournal of Neurochemistry
    Volume78
    Issue number3
    DOIs
    Publication statusPublished - 2001

    Fingerprint

    Pituitary Adenylate Cyclase-Activating Polypeptide
    Circadian Clocks
    Cell culture
    Clocks
    Cell Culture Techniques
    Genes
    Calcium
    Calcium-Calmodulin-Dependent Protein Kinase Type 2
    Mitogen-Activated Protein Kinase Kinases
    Tissue
    Cyclic AMP-Dependent Protein Kinases
    Messenger RNA
    Calcium-Calmodulin-Dependent Protein Kinase Type 4
    Suprachiasmatic Nucleus
    Primary Cell Culture
    Depolarization
    Calmodulin
    Nifedipine
    Protein Kinase Inhibitors
    Gene expression

    Keywords

    • Cerebellum
    • Circadian
    • Granule cell culture
    • mPer1
    • PACAP
    • Signal transduction

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

    Cite this

    Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture. / Akiyama, Masashi; Minami, Youichi; Nakajima, Tatsuki; Moriya, Takahiro; Shibata, Shigenobu.

    In: Journal of Neurochemistry, Vol. 78, No. 3, 2001, p. 499-508.

    Research output: Contribution to journalArticle

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    AU - Moriya, Takahiro

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