BCL-2 Modifying Factor (BMF) Is a Central Regulator of Anoikis in Human Intestinal Epithelial Cells
| Autor: | Helen M. Becker, Claudia Hofmann, Christian Ploner, Stephan Kiessling, Florian Obermeier, Martin Hausmann, Katharina Leucht, Andreas Villunger, Michael Fried, Gerhard Rogler, Michaela Krebs, Jürgen Schölmerich, Silvia Kellermeier, Werner Falk |
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| Přispěvatelé: | University of Zurich, Hausmann, M |
| Rok vydání: | 2011 |
| Předmět: |
1303 Biochemistry
Cell Survival Cell 610 Medicine & health Caspase 3 Biology digestive system Biochemistry 1307 Cell Biology Mice Bcl-2-Modifying Factor Intestinal mucosa Western blot Cell Adhesion 1312 Molecular Biology medicine Animals Humans Anoikis Intestinal Mucosa Molecular Biology Adaptor Proteins Signal Transducing Mice Knockout Gene knockdown medicine.diagnostic_test Dextran Sulfate Epithelial Cells Cell Biology Colitis Molecular biology Up-Regulation 10219 Clinic for Gastroenterology and Hepatology medicine.anatomical_structure Apoptosis Gene Knockdown Techniques 10076 Center for Integrative Human Physiology Acute Disease 570 Life sciences biology Proto-Oncogene Proteins c-akt |
| Zdroj: | Journal of Biological Chemistry. 286:26533-26540 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.265322 |
| Popis: | BCL-2 modifying factor (BMF) is a sentinel considered to register damage at the cytoskeleton and to convey a death signal to B-cell lymphoma 2. B-cell lymphoma 2 is neutralized by BMF and thereby facilitates cytochrome C release from mitochondria. We investigated the role of BMF for intestinal epithelial cell (IEC) homeostasis. Acute colitis was induced in Bmf-deficient mice (Bmf(-/-)) with dextran sulfate sodium. Colonic crypt length in Bmf(-/-) mice was significantly increased as compared with WT mice. Dextran sulfate sodium induced less signs of colitis in Bmf(-/-) mice, as weight loss was reduced compared with the WT. Primary human IEC exhibited increased BMF in the extrusion zone. Quantitative PCR showed a significant up-regulation of BMF expression after initiation of anoikis in primary human IEC. BMF was found on mitochondria during anoikis, as demonstrated by Western blot analysis. RNAi mediated knockdown of BMF reduced the number of apoptotic cells and led to reduced caspase 3 activity. A significant increase in phospho-AKT was determined after RNAi treatment. BMF knockdown supports survival of IEC. BMF is induced in human IEC by the loss of cell attachment and is likely to play an important role in the regulation of IEC survival. |
| Databáze: | OpenAIRE |
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