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(In Japanese)脳を知る 脳膜神経相関の分子機構

Research report code R990004317
Posted date Feb 6, 2001
  • (In Japanese)裏出 良博
  • (In Japanese)(財)大阪バイオサイエンス研究所
Research organization
  • (In Japanese)(財)大阪バイオサイエンス研究所
Report name (In Japanese)脳を知る 脳膜神経相関の分子機構
Technology summary (In Japanese)本研究では、脳膜神経相関の分子機構を扱った。脳膜(クモ膜)は、従来は、脳脊髄を取り囲む単なる保護膜と考えられていたが、本研究において、内因性睡眠物質〔プロスタグランジン(PG)D2〕の合成酵素(リポカリン型PGD合成酵素)が、主にクモ膜で生産されて脳脊髄液に分泌されることを発見した。これによれば、脳膜は脳脊髄液を介して脳の機能維持に関与していることが予想される。我々は初年度において、PGD合成酵素が活性型ビタミンAや甲状腺ホルモンを結合し、これら疎水性生理活性物質の脳内輸送蛋白質として機能する可能性を示した。また、本酵素の遺伝子欠損マウスにおいて、痛覚反応などの中枢性機能異常を示すことを見い出した。更に、ヒト脳脊髄液における本酵素の濃度がくも膜下出血等の疾患において上昇することや、本酵素がヒト心臓でも生産され、冠状動脈血管の狭窄部位に蓄積し、血流中に放出されることを発見した。
Research field
  • Function of cell components
  • Animal physiology in general
  • Biological function
  • Research methods in biological sciences in general
Published papers related (In Japanese)(1)Y. Tokugawa, I. Kunishige, Y. Kubota, K. Shimoya, T. Nobunaga, T. Kimura, F. Saji, Y. Murata, N. Eguchi, H. Oda, Y. Urade, and O. Hayaishi: Lipocalintype prostaglandin D synthase in human male reproductive organs and seminal plasma. Biol. Reprod., 58, 600-607 (1998)
(2)D. Gerashchenko, C.T. Beuckmann, V.L. Marcheselli, W.C. Gordon, Y. Kanaoka, N. Eguchi, Y. Urade, O. Hayaishi, and N.G. Bazan: Localization of lipocalin-type prostanoid D synthase (β-trace) in iris, cilliary body, and eye fluids. Invest. Ophthalmol. Vis. Sci., 39, 198-203 (1998)
(3)A. Hiraoka, T. Arato, I. Tominaga, N. Eguchi, and Y. Urade: Sodium dodecyl sulfate capillary electrophoretic analysis of molecular mass heterogeneity of β-trace protein in cerebrospinal fluid from patients with central nervous system diseases. J. Chromatogr., 802, 143-148 (1998)
(4)R.L. Gerena, D. Irikura, Y. Urade, N. Eguchi, D.A. Chapman, and G.J. Killian: Identification of a fertility-associated protein in bull seminal plasma as lipocalin-type prostaglandin D synthase. Biol. Reprod., 58, 826-833 (1998)
(5)L.F. Garcia-Fernandez, Y. Urade, O. Hayaishi, J. Bernal, and A. Munoz: Identification of a thyroid hormone response element in the promoter region of the rat lipocalin-type prostaglandin D synthase (beta-trace) gene. Mol. Brain Res., 55, 321-330 (1998)
(6)T. Scammell, D. Gerashchenko, Y. Urade, H. Onoe, C. Saper, and O. Hayaishi: Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2. Proc. Natl. Acad. Sci., USA, 93, 5980-5984 (1998)
(7)D. Gerashchenko, C.T. Beuckmann, Y. Kanaoka, N. Eguchi, W.C. Gordon, Y. Urade, N.G. Bazan, and O. Hayaishi: Dominant expression of rat prostanoid DP receptor mRNA in leptomeninges, inner segments of photoreceptor cells, iris epithelium, and cilliary processes. J. Neurochem., 71, 937-945 (1998)
(8)B.K. Kubata, N. Eguchi, Y. Urade, K. Yamashita, T. Horii, and O. Hayaishi: Evidence of prostaglandin production by the human malaria parasite, Plasmodium falciparum. S. Afr. J. Sci., 94, 285-286 (1998)
(9)B.K. Kubata, N. Eguchi, Y. Urade, K. Yamashita, T. Mitamura, K. Tai, O. Hayaishi, and T. Horii: Plasmodium falciparum produces prostaglandins that are pyrogenic, somnogenic and immunosupressive substances in human. J. Exp. Med., 188, 1197-1202 (1998)
(10)N. Eguchi, T. Minami, N. Shirafuji, Y. Kanaoka, T. Tanaka, A. Nagata, N. Yoshida, Y. Urade, S. Ito, and O. Hayaishi: Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice. Proc. Natl. Acad. Sci. USA, 96, 726-730 (1999)
(11)M. Taniike, I. Mohri, N. Eguchi, D. Irikura, Y. Urade, K. Suzuki, and S. Okada: An apoptotic depletion of oligodendrocytes in the twitcher, a murine model of globoid cell leukodystrophy. J. Neurophathol. Exp. Neurol., 58, 644-653, (1999)
(12) Mase, M., Yamada, K., Iwata, A., Matsumoto, T, Seiki, K., Oda, H., and Urade, Y.: Acute and transient increase of lipocaliln-type prostaglandin D synthase (β-trace) level in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage. Neurosci. Lett. , 2 70, 188-190, (1999)
(13) Beuckmann, C.T., Aoyagi, M., Okazaki, I., Hiroike, T., Toh, H., Hayaishi, O. and Urade, Y. Binding of biliverdin, bilirubin, and thyroid hormones to lipocalin-type prostaglandin D synthase. Biochemistry, 38, 8006-8013, (1999)
(14) Inui, T., Ohkubo, T., Urade,Y., and Hayaishi, O. : Enhancement of lipocalin-type prostaglandin D synthase enzyme activity by guanidine hydrochloride. Biochem. Biophys. Res. Commun., 266, 641-646, (1999)
(15) Kuwamoto, K., Miyauchi-Hashimoto, H., Tanaka, K., Eguchi, N., Inui, T., Urade, Y., and Horio, T.: Possible involvement of enhanced prostaglandin E2 production in the photosensitivity in xerodema pigmentosum group a model mice. J. Invest. Dermatol., 114, 241-246, 2000
(16) Matsuoka, T., Hirata, M., Tanaka, H., Takahashi, Y., Murata, T., Kabashima, K., Sugimoto, Y., Kobayashi, T., Ushikubi, F., Aze, Y., Eguchi, N., Urade, Y., Yoshida, N., Kimura, K., Mizoguchi, A., Honda, Y., Nagai, H. and Narumiya, S. : Prostaglandin D2 as a mediator of allergic asthma. Science, 287, 2013-2016, 2000
(17)Pinzar, E., Kanaoka, Y., Inui, T., Eguchi, N., Urade, Y. and Hayaishi, O.: Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep. Proc. Natl. Acad. Sci. USA 97, 4903-4907, 2000
(18) Urade, Y. and Hayaishi, O.: Prostaglandin D synthase: Structure and Function. Vitam. Horm. 58, 89-120, 2000
Research project
  • Core Research for Evolutional Science and Technology;Understanding the Brain
Information research report
  • (In Japanese)裏出 良博. 脳を知る 脳膜神経相関の分子機構. 戦略的基礎研究推進事業 平成10年度 研究年報,1999. p.666 - 669.