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한빛사논문, 상위피인용논문
- 조회7,188
Mol. Cell, Vol 15, 355-366, 13 August 2004
BI-1 Regulates an Apoptosis Pathway Linked to Endoplasmic Reticulum Stress
Abstract
Han-Jung Chae 1, Hyung-Ryong Kim 1, Chunyan Xu 1, Beatrice Bailly-Maitre 1, Maryla Krajewska 1, Stan Krajewski 1, Steven Banares 1, Janice Cui 1, Murat Digicaylioglu 1, Ning Ke 1, Shinichi Kitada 1, Edward Monosov 1, Michael Thomas 1, Christina L. Kress 1, Jeremy R. Babendure 3, Roger Y. Tsien 2,3, Stuart A. Lipton 1, and John C. Reed 1
1The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 USA
2Department of Chemistry and Biochemistry, University of California, San Diego, University of California, San Diego, 310 CMM West, 9500 Gilman, La Jolla, CA 92093 USA
3Howard Hughes Medical Institute, University of California, San Diego, 310 CMM West, 9500 Gilman, La Jolla, CA 92093 USA
Correspondence: John C. Reed
858-646-3140 (phone)
858-646-3194 (fax)
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.
1The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 USA
2Department of Chemistry and Biochemistry, University of California, San Diego, University of California, San Diego, 310 CMM West, 9500 Gilman, La Jolla, CA 92093 USA
3Howard Hughes Medical Institute, University of California, San Diego, 310 CMM West, 9500 Gilman, La Jolla, CA 92093 USA
Correspondence: John C. Reed
858-646-3140 (phone)
858-646-3194 (fax)
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.
논문정보
- Research article
- 2004년 08월 (BRIC 등록일 )
- 국외 연구진
- 의약학 > 약학
- 120회 이상 인용된 논문 (상위피인용논문 등록일 2010-02-24)
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