BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress
BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress
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DOI：
10.1016/j.molcel.2004.06.038
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发表时间：
2004-08-13
期刊：
影响因子：
16
通讯作者：
Reed, JC
中科院分区：
文献类型：
--
作者：
Chae, HJ;Kim, HR;Reed, JC
Bax抑制剂-1（BI-1）是一种进化上保守的内质网（ER）蛋白，在动物和植物细胞中抑制细胞死亡。我们对bi-1基因被切除的小鼠进行了表征。来自BI-1缺陷小鼠的细胞，包括成纤维细胞、肝细胞和神经元，显示出对ER应激剂（毒胡萝卜素、衣霉素、布雷菲德菌素A）诱导的细胞凋亡的选择性超敏反应，但对线粒体或TNF/Fas死亡受体细胞凋亡途径的刺激剂不显示出选择性超敏反应。相反，BI-1过表达可防止ER应激诱导的细胞凋亡。BI-1介导的对ER应激诱导的细胞凋亡的保护与Bax活化和易位至线粒体的抑制、线粒体膜电位的保存和半胱天冬酶活化的抑制相关。BI-1过表达还减少了ER的可释放Ca 2+。在体内，bi-1（-/-）小鼠表现出对触发ER应激的刺激（包括中风和衣霉素注射）诱导的组织损伤的敏感性增加。因此，BI-1调节ER应激期间细胞保存的重要细胞死亡途径。
Bax inhibitor-1 (BI-1) is an evolutionarily conserved endoplasmic reticulum (ER) protein that suppresses cell death in both animal and plant cells. We characterized mice in which the bi-1 gene was ablated. Cells from BI-1-deficient mice, including fibroblasts, hepatocytes, and neurons, display selective hypersensitivity to apoptosis induced by ER stress agents (thapsigargin, tunicamycin, brefeldin A), but not to stimulators of mitochondrial or TNF/Fas-death receptor apoptosis pathways. Conversely, BI-1 overexpression protects against apoptosis induced by ER stress. BI-1-mediated protection from apoptosis induced by ER stress correlated with inhibition of Bax activation and translocation to mitochondria, preservation of mitochondrial membrane potential, and suppression of caspase activation. BI-1 overexpression also reduces releasable Ca2+ from the ER. In vivo, bi-1(-/-) mice exhibit increased sensitivity to tissue damage induced by stimuli that trigger ER stress, including stroke and tunicamycin injection. Thus, BI-1 regulates a cell death pathway important for cytopreservation during ER stress.