BI-1 Regulates an Apoptosis Pathway Linked to Endoplasmic Reticulum Stress
2004; Elsevier BV; Volume: 15; Issue: 3 Linguagem: Inglês
10.1016/j.molcel.2004.06.038
ISSN1097-4164
AutoresHan‐Jung Chae, Hyung‐Ryong Kim, Chunyan Xu, Béatrice Bailly-Maître, Maryla Krajewska, Stan Krajewski, Steven Banares, Janice Cui, Murat Digicaylioglu, Ke Ning, Shinichi Kitada, Edward Monosov, Michaël Thomas, Christina Kress, Jeremy R. Babendure, Roger Y. Tsien, Stuart A. Lipton, John C. Reed,
Tópico(s)Autophagy in Disease and Therapy
ResumoBax 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 Ca(2+) 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.
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