FAS/TNF R1 INITIATED HEPATOCYTE DEATH IN MEDIATE BY BID

描述：(摘自摘要)程序性细胞死亡，或称细胞凋亡是一种 发育中的基本生物学过程和体内的动态平衡控制 所有的多细胞生物。细胞凋亡调控的紊乱可能 会导致癌症或自身免疫等疾病。细胞凋亡途径 包括在细胞表面作为受体分子的成分 对于死亡信号，如Fas或肿瘤坏死因子受体1.死亡的参与 受体导致半胱氨酸天冬氨酸酶的招募和随后的激活 死亡路径中的中央执行者。然而，其他死亡信号，如 放化疗药物可能通过诱导释放激活半胱氨酸天冬氨酸酶 线粒体中的细胞色素c。线粒体途径很容易受到 Bcl2家族蛋白的调控。这个组织中支持细胞凋亡的成员 家族(Bid或Bax)可诱导细胞色素c释放，而抗细胞凋亡 该家族成员(Bcl2或Bclxl)可抑制其释放。最近它 已有研究表明，由Fas或TNF-R1启动的胞浆途径可以是 通过Bid连接到线粒体途径，Bid是促进细胞凋亡的成员 BCL-2家族。更重要的是，这种联系似乎起到了至关重要的作用 Fas/TNF-R1在诱导肝细胞凋亡中的作用 激活。申请者之前已经产生了一个投标缺陷的动物模型 因此拟利用该模型来研究：1)Bid在Fas/TNF-R1中的作用 -体内肝损伤；2)Bid诱导的线粒体事件 肝细胞凋亡；3)Bid调控的分子机制 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.