Abstract | BACKGROUND & AIMS: Members of the bcl-2 family of proteins are important determinants of cell fate. Bcl-2 and bcl-w have previously been identified as antiapoptotic members of this family that promote gastrointestinal epithelial cell survival. However, a proapoptotic family member that exerts important effects in the gastrointestinal tract has not yet been identified. We have therefore investigated intestinal epithelial apoptosis in bak-null mice. METHODS: Apoptosis, mitosis, differentiated cell composition, and cell number were assessed on a cell positional basis in the small intestinal and colonic epithelia of bak-null mice and their C57BL/6 wild-type counterparts. Apoptosis was induced by 1-Gy gamma-irradiation or 10mg/kg azoxymethane (AOM). Aberrant crypt foci were induced by 3 weekly injections of 10mg/kg AOM. RESULTS: The amount of spontaneous apoptosis in the colonic intercrypt table was reduced, and colonic crypt cell number and mitotic index were elevated in bak-null mice relative to C57BL/6 wild-type mice. Bak-null colonic crypts contained more goblet cells and fewer endocrine cells than those from C57BL/6 mice. Fewer colonic epithelial apoptotic cells were observed after gamma-radiation and AOM in bak-null mice, and these mice also displayed greater numbers of colonic AOM-induced aberrant crypt foci. None of these parameters differed in the small intestinal epithelium of bak-null mice compared with C57BL/6. CONCLUSIONS: Bak prevents colonic crypt hyperplasia by regulating spontaneous apoptosis at the colonic intercrypt table region and also regulates damage-induced apoptosis in the colonic crypt. Deletion of bak in vivo results in altered colonic proliferation and differentiation, and causes increased susceptibility to colonic carcinogenesis.
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Authors | Carrie A Duckworth, D Mark Pritchard |
Journal | Gastroenterology
(Gastroenterology)
Vol. 136
Issue 3
Pg. 943-52
(Mar 2009)
ISSN: 1528-0012 [Electronic] United States |
PMID | 19185578
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bak1 protein, mouse
- bcl-2 Homologous Antagonist-Killer Protein
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Topics |
- Animals
- Apoptosis
(physiology)
- Cell Count
- Cell Differentiation
(physiology)
- Cell Division
(physiology, radiation effects)
- Colon
(pathology, physiology)
- Colonic Neoplasms
(pathology, physiopathology)
- Enteroendocrine Cells
(pathology, physiology)
- Female
- Gamma Rays
- Goblet Cells
(pathology, physiology)
- Hyperplasia
- Immunohistochemistry
- Intestinal Mucosa
(pathology, physiology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Mitosis
(physiology, radiation effects)
- bcl-2 Homologous Antagonist-Killer Protein
(genetics, metabolism)
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