FAS/TNF R1 INITIATED HEPATOCYTE DEATH IN MEDIATE BY BID

描述：（来自摘要）程序性细胞死亡，或凋亡是一种 发育中的基本生物过程和体内平衡控制 所有的多细胞生物。细胞凋亡调节的紊乱可能 导致癌症或自身免疫等疾病。凋亡途径 包括位于细胞表面并作为受体分子的成分 死亡信号，如Fas或TNF受体1。死亡的约定 受体导致半胱天冬酶的募集和随后的激活， 死亡通道的中央执行者然而，其他死亡信号，如 放疗和化疗药物可以通过诱导caspase的释放来激活caspase 细胞色素c的含量。线粒体途径易受 Bcl-2家族蛋白的调节。这其中的促凋亡成员 Bax家族（Bid或Bax）可诱导细胞色素c的释放，而抗细胞凋亡的 家族成员（Bcl-2或Bcl-xL）可以抑制其释放。最近它 已经表明，由Fas或TNF-R1启动的胞质途径可以被 通过Bid与线粒体途径相连，Bid是线粒体的促凋亡成员。 Bcl-2家族更重要的是，这种联系似乎对 Fas/TNF-R1介导的肝细胞凋亡 activation.申请人之前已经生成了一个出价不足的动物模型 本研究拟利用该模型研究：1）Bid在Fas/TNF-R1中的作用 - 在体内引发的肝损伤; 2）由Bid诱导的线粒体事件 Bid对肝细胞凋亡的影响; 3）Bid调节肝细胞凋亡的分子机制 线粒体凋亡事件。

Description: (From abstract) Programmed cell death, or apoptosis is a fundamental biological process in development and homeostasis control within all multicellular organisms. Disturbances in the regulation of apoptosis may result in diseases such as cancer or autoimmunity. The apoptosis pathways include components that are at the cell surface and serve as receptor molecules for death signals, such as Fas or TNF-receptor 1. The engagement of the death receptors leads to recruitment and subsequent activation of caspases, the central executors in the death pathway. However, other death signals, such as radiation and chemotherapeutic drugs may activate caspases by inducing release of cytochrome c from mitochondria. The mitochondrial pathway is susceptible to the regulation of Bcl-2 family proteins. The pro-apoptosis members of this family (Bid or Bax) can induce cytochrome c release, whereas the anti-apoptosis members of the family (Bcl-2 or Bcl-xL) can inhibit its release. Recently it has been shown that the cytosolic pathway initiated by Fas or TNF-R1 can be linked to the mitochondrial pathway via Bid, a pro-apoptosis member of the Bcl-2 family. More importantly, it seems that this connection plays a critical role in the development of hepatocyte apoptosis induced by Fas/TNF-R1 activation. The applicant has previously generated a bid-deficient animal model and thus intend to use this model to study: 1) the role of Bid in Fas/TNF-R1 -initiated hepatic injury in vivo; 2) the mitochondrial events induced by Bid in hepatocyte apoptosis; 3) the molecular mechanisms of Bid in regulating mitochondrial apoptotic events.