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MOLECULAR MECHANISMS OF PROGRAMMED CELL DEATH BY ECDYSTEROID IN BOMBYX ANTERIOR SILK GLAND

家蚕前丝腺脱皮类固醇程序性细胞死亡的分子机制

基本信息

批准号：
14360033
负责人：
SAKURAI Sho
金额：
$ 9.28万
依托单位：
KANAZAWA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Programmed cell death (PCD) of anterior silk glands of the silkworm, Bombyx mori, is induced by 20E elicits its effects via binding with a heterodimeric nuclear receptor (EcR/USP) and acting as a transcriptional factor. In the PCD, however, we found various events associated with the cell death, which cannot be interpreted from the point of view of 20E action via nuclear receptor, and therefore we assumed the presence of a non-genomic action of 20E via ecdysone membrane receptor (mEcR). We confirmed the presence of the binding sites of ecdysteroids on membrane proteins. The responsible protein is embedded in plasma membrane and possesses a high binding activity with ecdysteroids. In addition, we found that 20E increases an intracellular cAMP level as rapidly as 30 seconds after 20E challenge. We also demonstrated that activation of protein kinase C and caspase 3 is involved in the 20E-induced PCD. The PCD precedes via plasma membrane blebbing, cellular shrinkage, DNA oligonucleosomal fragmentation, nuclear condensation, nuclear fragmentation and apoptotic body formation. Blebbing, cell shrinkage and apoptotic body formation are under the control of genomic action of 20E while other events are under the non-genomic action of 20E, probably through mEcR. The present results suggest that a single steroid hormone exerts its physiological effects through both genomic and nongenomic pathways.

20 E通过与异源二聚体核受体（EcR/USP）结合并作为转录因子发挥作用，诱导家蚕前丝腺细胞程序性死亡（PCD）。然而，在PCD中，我们发现了与细胞死亡相关的各种事件，这些事件不能从20 E通过核受体作用的角度来解释，因此我们假设20 E通过蜕皮激素膜受体（mEcR）的非基因组作用的存在。我们证实了蜕皮甾体的膜蛋白上的结合位点的存在。负责蛋白包埋在质膜上，并具有与蜕皮甾体的高结合活性。此外，我们发现，20 E增加细胞内cAMP水平迅速为30秒后，20 E的挑战。我们还证明了蛋白激酶C和caspase 3的激活参与了20 E诱导的PCD。PCD通过质膜起泡、细胞皱缩、DNA寡核体断裂、核浓缩、核碎裂和凋亡小体形成进行。起泡、细胞收缩和凋亡小体形成受20 E的基因组作用控制，而其他事件可能通过mEcR受20 E的非基因组作用控制。目前的研究结果表明，一个单一的类固醇激素通过基因组和非基因组途径发挥其生理作用。