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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cho, Ssang-goo Ha, Ki-chan Chae, Han-jung Ahn, Taeho Kim, Sanguk Chae, Soo-wan Kim, Hyung-ryong Lee, Geum-hwa Seo, Young-rok Lee, Bong-jin Moon, Ji-yong Shin, Yong-joo Reed, John C. |
| Description | Author Affiliation: Kim HR ( Department of Dental Pharmacology and Wonkwang Biomaterial Implant Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk 570-749, Republic of Korea.) |
| Abstract | In this study, Bax inhibitor-1 (BI-1) overexpression reduces the ER pool of Ca(2+) released by thapsigargin. Cells overexpressing BI-1 also showed lower intracellular Ca(2+) release induced by the Ca(2+) ionophore ionomycin as well as agonists of ryanodine receptors and inositol trisphosphate receptors. In contrast, cells expressing carboxyl-terminal deleted BI-1 (CDelta-BI-1 cells) displayed normal intracellular Ca(2+) mobilization. Basal Ca(2+) release rates from the ER were higher in BI-1-overexpressing cells than in control or CDelta-BI-1 cells. We determined that the carboxyl-terminal cytosolic region of BI-1 contains a lysine-rich motif (EKDKKKEKK) resembling the pH-sensing domains of ion channels. Acidic conditions triggered more extensive Ca(2+) release from ER microsomes from BI-1-overexpressing cells and BI-1-reconstituted liposomes. Acidic conditions also induced BI-1 protein oligomerization. Interestingly subjecting BI-1-overexpressing cells to acidic conditions induced more Bax recruitment to mitochondria, more cytochrome c release from mitochondria, and more cell death. These findings suggest that BI-1 increases Ca(2+) leak rates from the ER through a mechanism that is dependent on pH and on the carboxyl-terminal cytosolic region of the BI-1 protein. The findings also reveal a cell death-promoting phenotype for BI-1 that is manifested under low pH conditions. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 23 |
| Volume Number | 283 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2008-06-06 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Regulatory Proteins Biosynthesis Calcium Metabolism Endoplasmic Reticulum Inositol 1,4,5-Trisphosphate Receptors Membrane Proteins Ryanodine Receptor Calcium Release Channel Amino Acid Motifs Physiology Animals Genetics Cytochromes c Enzyme Inhibitors Pharmacology Gene Expression HeLa Cells Hydrogen-Ion Concentration Microsomes Mitochondria Protein Structure, Tertiary Thapsigargin Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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