BCL-2 Modifying Factor (BMF) Is a Central Regulator of Anoikis in Human Intestinal Epithelial Cells

Hausmann, Martin and Leucht, Katharina and Ploner, Christian and Kiessling, Stephan and Villunger, Andreas and Becker, Helen and Hofmann, Claudia and Falk, Werner and Krebs, Michaela and Kellermeier, Silvia and Fried, Michael and Schoelmerich, Juergen and Obermeier, Florian and Rogler, Gerhard (2011) BCL-2 Modifying Factor (BMF) Is a Central Regulator of Anoikis in Human Intestinal Epithelial Cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 286 (30). pp. 26533-26540. ISSN 0021-9258,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: INDUCED APOPTOSIS-ANOIKIS; CRYPT-VILLUS AXIS; DIFFERENTIAL EXPRESSION; BREAST-CANCER; MOTOR COMPLEX; IN-SITU; CASPASES; ACTIVATION; MUCOSA; BIM;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Jun 2020 05:40
Last Modified: 05 Jun 2020 05:40
URI: https://pred.uni-regensburg.de/id/eprint/20520

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