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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-59846

Hausmann, M; Leucht, K; Ploner, C; Kiessling, S; Villunger, A; Becker, H; Hofmann, C; Falk, W; Krebs, M; Kellermeier, S; Fried, M; Schölmerich, J; Obermeier, F; Rogler, G (2011). BCL-2 modifying factor (BMF) is a central regulator of anoikis in human intestinal epithelial cells. Journal of Biological Chemistry, 286(30):26533-26540.

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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.

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9 citations in Web of Science®
10 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:July 2011
Deposited On:25 Feb 2012 21:47
Last Modified:05 Dec 2013 07:55
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Hausmann, M; Leucht, K; Ploner, C; Kiessling, S; Villunger, A; Becker, H; Hofmann, C; Falk, W; Krebs, M; Kellermeier, S; Fried, M; Schölmerich, J; Obermeier, F; Rogler, G (2011). BCL-2 modifying factor (BMF) is a central regulator of anoikis in human intestinal epithelial cells. Journal of Biological Chemistry, 286(30):26533-26540. © the American Society for Biochemistry and Molecular Biology.
Publisher DOI:10.1074/jbc.M111.265322
PubMed ID:21673109

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