Molecular mechanisms underlying the control of programmed cell death induced by 20-hydroxyecdysone in Bombyx anterior silk gland: 20E action from genomic to non-genomic

报告主题：Molecular mechanisms underlying the control of programmed cell death induced by 20-hydroxyecdysone in Bombyx anterior silk gland: 20E action from genomic to non-genomic
报 告 人: Prof.?Sho Sakurai（櫻井 勝），Ph.D
日本国立金沢大学 副校长
金沢大学理学部生物科学系 教授
报告时间: 2011年7月8日 上午9:00
报告地点: 苏州大学独墅湖校区图书馆825

主要简历：
東京農工大学農学部農芸化学科(1969)
東京大学理学硕士 (1973)
東京大学理学博士 (1976)
日本振兴学术协会博士后奖学金（1976-1978）
美国哈佛大学生物学实验室 副研究员(1978-1980)
金沢大学理学部生物系 副教授(1981-1992)
美国北卡罗来纳大学生物系 特聘副教授(1985-1987)
日本金沢大学理学部生物科学系，自然科学研究科教授(1992)
日本金沢大学副校长(2007)

主要研究方向：细胞凋亡与信号传导、昆虫蜕皮激素与滞育的内分泌调节等

在FEBS J, Dev. Genes Evol， Mol Cell Endocrinol, J Insect Physiol, Appl. Entomol. Zool，Zoolog Sci，Insect Mol. Biol.，Insect Biochem Mol Biol，Eur J Biochem等著名国际期刊上发表论文50余篇。近期发表论文：

Matsui H, Kakei M, Iwami M, Sakurai S. Glucose oxidase prevents programmed cell death of the silkworm anterior silk gland through hydrogen peroxide production. FEBS J. 2011, 278(5):776-85.
Iga M, Manaboon M, Matsui H, Sakurai S. Ca2+-PKC-caspase 3-like protease pathway mediates DNA and nuclear fragmentation in ecdysteroid-induced programmed cell death. Mol Cell Endocrinol. 2010 , 321(2):146-51.
Manaboon M, Iga M, Iwami M, Sakurai S.Intracellular mobilization of Ca2+ by the insect steroid hormone 20-hydroxyecdysone during programmed cell death in silkworm anterior silk glands.J Insect Physiol. 2009, 55(2):122-8.
Nujira Tatun, Tippawan Singtripop, Shingo Osugi, Na Chiangmai Siriluk, Masafumi Iwami, and Sho Sakurai . Possible involvement of proteinaceous and non-proteinaceous trehalase inhibitors in the regulation of hemolymph trehalose concentration in Bombyx mori. Appl. Entomol. Zool., 2009,44 (1), 85-94.
Elmogy M, Iwami M, Sakurai S.Solubilization of the ecdysone binding protein from anterior silk gland cell membranes of the silkworm, Bombyx mori.Zoolog Sci. 2007, 24(10):971-7.
Iga M, Iwami M, Sakurai S.Nongenomic action of an insect steroid hormone in steroid-induced programmed cell death. Mol Cell Endocrinol. 2007 Jan 15;263(1-2):18-28.
Takayuki Sekimoto, Masafumi Iwami, and Sho Sakurai. Hormonal regulation of two isoforms of Ets transcription factor E74 gene in programmed cell death in the silkworm anterior silk gland. Insect Mol. Biol., 2007, 16 (5), 581-590.
Elmogy M, Terashima J, Iga M, Iwami M, Sakurai S.A rapid increase in cAMP in response to 20-hydroxyecdysone in the anterior silk glands of the silkworm, Bombyx mori. Zoolog Sci. 2006, 23(8):715-9.
Kaneko Y, Takaki K, Iwami M, Sakurai S.Developmental profile of annexin IX and its possible role in programmed cell death of the Bombyx mori anterior silk gland. Zoolog Sci. 2006, 23(6):533-42.
Takayuki Sekimoto, Masafumi Iwami, and Sho Sakurai. Coordinate responses of transcription factors to ecdysone during programmed cell death in the anterior silk gland of the silkworm, Bombyx mori. Insect Mol. Biol., 2006, 15 (3), 281-292.
Oda Y, Iwami M, Sakurai S.Membrane-bound sorbitol 6-phosphatase in fat body cells controls the dynamics of sorbitol 6-phosphate, a major hemolymph sugar in the silkworm.Insect Biochem Mol Biol. 2005, 35(11):1289-92.
Kakei M, Iwami M, Sakurai S.Death commitment in the anterior silk gland of the silkworm, Bombyx mori.J Insect Physiol. 2005, 51(1):17-25.
Elmogy M, Iwami M, Sakurai S.Presence of membrane ecdysone receptor in the anterior silk gland of the silkworm Bombyx mori. Eur J Biochem. 2004, 271(15): 3171-9.
Koyama T, Iwami M, Sakurai S.Ecdysteroid control of cell cycle and cellular commitment in insect wing imaginal discs.Mol Cell Endocrinol. 2004, 213(2):155-66.
Koyama T, Obara Y, Iwami M, Sakurai S.Commencement of pupal commitment in late penultimate instar and its hormonal control in wing imaginal discs of the silkworm, Bombyx mori. J Insect Physiol. 2004, 50(2-3):123-33.
Takaki K, Sakurai S. Regulation of prothoracic gland ecdysteroidogenic activity leading to pupal metamorphosis.Insect Biochem Mol Biol. 2003, 33(12):1189-99.
Singtripop, T., Tungjitwitayakul, T. and Sakurai, S. Intensity of larval diapause in the bamboo borer, Omphisa fuscidentalis，Zool. Sci.，(2002, 19, 5 : 577-582
Singtripop, T., Oda, Y., Wanichacheewa, S. and Sakurai, S. Sensitivities to juvenile hormone and ecdysteroid in the diapause larvae of Omphisa fuscidentalis based on the hemolymph trehalose dynamics index.，J. Insect Physiol., 2002, 48(8):817-824.
Yoshikazu Obara, Mayumi Miyatani, Yoko Ishiguro, Kaori Hirota, Takeshi Koyama, Susumu Izumi, Masafumi Iwami, and Sho Sakurai. Pupal commitment and its hormonal control in wing imaginal discs. J. Insect Physiol., 2002. 48 (10), 933-944.
Yoshikazu Obara, Mayumi Miyatani, Yoko Ishiguro, Kaori Hirota, Takeshi Koyama, Susumu Izumi, Masafumi Iwami, and Sho Sakurai. Pupal commitment and its hormonal control in wing imaginal discs. J. Insect Physiol., 2002, 48 (10), 933-944.
Tsuzuki, S., Iwami, M. and Sakurai, S. Ecdysteroid-inducible genes in the programmed cell death during insect metamorphosis，Insect Biochem. Molec. Biol., 2001, 31：321-331
Terashima, J., Yasuhara, M., Iwami, M. and Sakurai, S.Programmed cell death triggered by insect steroid hormone, 20-hydroxyecdysone, in the anterior silk gland of the silkworm, Bombyx mori，Dev. Genes Evol, 2001, 2,10: 545-558

报告摘要: Silk gland of Bombyx mori is a larval specific tissue that degenerates at the time of pupation through programmed cell death. The death is triggered by the metamorphic rise of hemolymph ecdysteroid concentration. The cell death is triggered by 20-hydroxyecdysone (20E) in vitro at the M, which is similar to the in vivo peat titer 2 days before?concentration of 1 pupation (2 days after the gut purge). When cultured with 20E, the glands undergo cell death with exhibiting sequential changes in cellular and nuclear morphology, beginning with cell dethatchment followed by cell shrinkage, DNA fragmentation, nuclear condensation, nuclear fragmentation and apoptotic body formation, in order. 20E induces hierarchical gene expression, including EcR, Ftz-F1, that results in cell shrinkage and apoptotic?Usp, E74, E75, BHR-3 and body formation. Beside the de novo gene expression, 20E acts through signal transducing pathways beginning with binding to a putative membrane ecdysone receptor (mEcR). Pharmacological studies using agonists, antagonists and inhibitors indicated that there are two pathways, which culminate in either DNA fragmentation and nuclear fragmentation or nuclear condensation. The former , IP3 binding to IP3R?pathway begins with activations of G-protein and then PLC on ER, Ca2+ release from ER, activation of PKC and then caspase-3-like protein. Nuclear condensation is induced through a calmodulin-CaMKII pathway, although the intracellular Ca2+ elevation does not activate CaMKII. In addition, the genomic and two non-genomic pathways affect each other though the interaction remains seen at all. In addition to the action of 20E, the cell death of the anterior silk gland is under self-control. The gland cells express glucose-oxidase (GOD) gene from the beginning of the fifth instar, and the oxidase protein is accumulated in the inner cavity of the gland. GOD catalyzes glucose to gluconolactone and produces hydrogen peroxide as a by-product. Hydrogen peroxide may be continuously produced through a feeding period. Hydrogen peroxide inhibits specifically the expression of genes described above, which eventually inhibits 20E action to trigger the cell death. At the onset of spinning, the GOD in the inner cavity is abandoned with releasing silk thread for constructing foothold before producing round cocoon. Thus, the glands become responsive to 20E with undergo the cell death. The glands must be committed to die before the onset of spinning, and the presence of death commitment and its timing will be discussed.