Prostaglandin F2α Affects the Cycle of Clock Gene Expression and Mouse Behavior

DOI Web Site 研究データあり 参考文献49件 オープンアクセス
  • Yuya Tsurudome
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Yuya Yoshida
    Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Kengo Hamamura
    Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Takashi Ogino
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Sai Yasukochi
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Shinobu Yasuo
    Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
  • Ayaka Iwamoto
    Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
  • Tatsuya Yoshihara
    SOUSEIKAI Fukuoka Mirai Hospital Clinical Research Center, 3-5-1 Kashiiteriha, Higashi-ku, Fukuoka 813-0017, Japan
  • Tomoaki Inazumi
    Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan
  • Soken Tsuchiya
    Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan
  • Toru Takeo
    Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan
  • Naomi Nakagata
    Division of Reproductive Biotechnology and Innovation, Center for Animal Resources and Development (CARD), Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan
  • Shigekazu Higuchi
    Department of Human Life Design and Science, Faculty of Design, Kyushu University, 4-9-1 Shiobaru, Minami-ku, Fukuoka 815-8540, Japan
  • Yukihiko Sugimoto
    Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan
  • Akito Tsuruta
    Department of Glocal Healthcare Science, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Satoru Koyanagi
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Naoya Matsunaga
    Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Shigehiro Ohdo
    Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

説明

<jats:p>Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor (Ptgfr) has no known relationship with biological rhythms. Here, we first measured the locomotor period lengths of Ptgfr-KO (B6.129-Ptgfrtm1Sna) mice and found that they were longer under constant dark conditions (DD) than those of wild-type (C57BL/6J) mice. We then investigated the clock gene patterns within the suprachiasmatic nucleus in Ptgfr-KO mice under DD and observed a decrease in the expression of the clock gene cryptochrome 1 (Cry1), which is related to the circadian cycle. Moreover, the expression of Cry1, Cry2, and Period2 (Per2) mRNA were significantly altered in the mouse liver in Ptgfr-KO mice under DD. In the wild-type mouse, the plasma prostaglandin F2α (PGF2α) levels showed a circadian rhythm under a 12 h cycle of light–dark conditions. In addition, in vitro experiments showed that the addition of PTGFR agonists altered the amplitude of Per2::luc activity, and this alteration differed with the timing of the agonist addition. These results lead us to hypothesize that the plasma rhythm of PGF2α is important for driving clock genes, thus suggesting the involvement of PGF2α- and Ptgfr-targeting drugs in the biological clock cycle.</jats:p>

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