Bax Inhibitor-1 Regulates Endoplasmic Reticulum Stress-associated Reactive Oxygen Species and Heme Oxygenase-1 Expression
| Autor: | John C. Reed, Christina L. Kress, Do-Sung Kim, Ki-Chan Ha, Geum-Hwa Lee, Mike Cuddy, Hyung-Ryong Kim, Soo-Wan Chae, Han-Jung Chae, Hyun-Kyung Kim |
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| Rok vydání: | 2007 |
| Předmět: |
Small interfering RNA
NF-E2-Related Factor 2 Fibrosarcoma Apoptosis DNA Fragmentation Oxidative phosphorylation Biology Endoplasmic Reticulum Biochemistry Cell Line Tumor Humans Initiation factor Promoter Regions Genetic Molecular Biology chemistry.chemical_classification Reactive oxygen species BAX inhibitor 1 Endoplasmic reticulum Membrane Proteins Cell Biology Carbocyanines Molecular biology Cell biology Heme oxygenase chemistry Unfolded protein response Stress Mechanical Apoptosis Regulatory Proteins Reactive Oxygen Species Heme Oxygenase-1 |
| Zdroj: | Journal of Biological Chemistry. 282:21618-21628 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m700053200 |
| Popis: | The Bax inhibitor-1 (BI-1) is an anti-apoptotic protein that is located in endoplasmic reticulum (ER) membranes and protects cells from ER stress-induced apoptosis. The ER is associated with generation of reactive oxygen species (ROS) through oxidative protein folding. This study examined the role of BI-1 in the regulation of ER stress-induced accumulation of ROS and expression of unfolded protein response-associated proteins. BI-1 reduced the expression levels of glucose response protein 78, C/EBP homologous protein, phospho-eukaryotic initiation factor 2alpha, IRE1alpha, XBP-1, and phospho-JNK and inhibited the cleavage of ATF-6alpha p-90, leading to the inhibition of ROS. Although ROS scavengers offer some protection against ER stress-induced apoptosis, the expression of pro-apoptotic ER stress proteins was not affected. This study shows that the response of unfolded proteins is followed by ROS accumulation under ER stress, which is regulated in BI-1 cells. The mechanism for these BI-1-associated functions involves the expression of heme oxygenase-1 (HO-1) through nuclear factor erythroid 2-related factor 2. In BI-1 cells, the transfection of HO-1 small interfering RNA completely abolished the BI-1-induced protection. The endogenous expression of HO-1 through ER stress-initiated ROS is believed to be as a protection signal. In conclusion, these observations suggest that BI-1 can inhibit the ER stress proteins as well as the accumulation of ROS, thereby protecting the cells. Moreover, HO-1 plays an important role in the BI-1-associated protection against ER stress. |
| Databáze: | OpenAIRE |
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