期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 48, 期 6, 页码 1105-1110出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2009.10.026
关键词
Endoplasmic reticulum; ER stress; Heart failure; Anti-cancer drug; Atherosclerosis; Plaque rupture
资金
- Ministry of Health, Labor, and Welfare-Japan
- Ministry of Education, Culture, Sports, Science, and Technology-Japan
- Japan Heart Foundation
- Japan Cardiovascular Research Foundation
The endoplasmic reticulum (ER) is an organelle involved in protein folding, calcium homeostasis, and lipid biosynthesis. Various factors that interfere with ER function lead to accumulation of unfolded proteins, including oxidative stress, ischemia, disturbance of calcium homeostasis, and overexpression of normal and/or incorrectly folded proteins. The resulting ER stress triggers the unfolded protein response (UPR) that induces signal transduction events to reduce the accumulation of unfolded proteins by increasing ER resident chaperones, inhibiting protein translation, and accelerating the degradation of unfolded proteins. However, if stress is severe and/or prolonged, the ER also initiates apoptotic signaling that includes induction of the proapoptotic transcriptional factor C/EBP homologous protein, activation of c-Jun amino-terminal kinase, and cleavage of caspase-12. These ER-initiated events lead to cell death via mitochondria-dependent and-independent apoptotic pathways. Furthermore, the B cell lymphoma 2 family of proteins expressed on the ER and mitochondria are also involved in regulating cell death due to ER stress. Thus, the ER is now recognized as a vitally important organelle that can decide cell survival or death. Recent animal and human studies have revealed that the UPR and ER-initiated apoptosis are implicated in the pathophysiology of various cardiovascular diseases, including heart failure, ischemic heart disease, the development of atherosclerosis, and plaque rupture. Improved understanding of the molecular mechanisms underlying UPR activation and ER-initiated apoptosis in cardiovascular disease will provide us with new targets for drug discovery and therapeutic intervention. (C) 2009 Elsevier Ltd. All rights reserved.
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