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  • American Physiological Society  (2)
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  • American Physiological Society  (2)
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  • 1
    Online Resource
    Online Resource
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Gastrointestinal and Liver Physiology Vol. 295, No. 4 ( 2008-10), p. G798-G805
    In: American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 295, No. 4 ( 2008-10), p. G798-G805
    Abstract: Elevated serum concentrations of the hormone gastrin are associated with the development of gastric carcinoid tumors, but the mechanisms of tumor development are not fully understood. We hypothesized that the antiapoptotic effects of gastrin may be implicated and have therefore investigated the role of antiapoptotic members of the bcl-2 family of proteins. AGS-G R human gastric carcinoma cells stably transfected with the CCK-2 receptor were used to assess changes in the expression of bcl-2 family members following gastrin treatment and the function of mcl-1 during apoptosis was investigated by use of small-interfering RNA (siRNA). Treatment of AGS-G R cells with 10 nM gastrin for 6 h caused maximally increased mcl-1 protein abundance. Gastrin-induced mcl-1 expression was inhibited by the transcription inhibitor actinomycin D and by the protein synthesis inhibitor cycloheximide. Downstream signaling of mcl-1 expression occurred via the CCK-2 receptor, protein kinase C, and MAP kinase pathways, but not via PI 3-kinase. Transfection with mcl-1 siRNA significantly suppressed mcl-1 protein expression and abolished the antiapoptotic effects of gastrin on serum starvation-induced apoptosis. Mcl-1 protein expression was also specifically increased in the type I enterochromaffin-like cell carcinoid tumors of 10 patients with autoimmune atrophic gastritis and hypergastrinemia. Gastrin therefore signals via the CCK-2 receptor, protein kinase C, and MAP kinase to induce expression of antiapoptotic mcl-1 in AGS-G R cells, and mcl-1 expression is also increased in human hypergastrinemia-associated type I gastric carcinoid tumors. Gastrin-induced mcl-1 expression may therefore be an important mechanism contributing toward type I gastric carcinoid development.
    Type of Medium: Online Resource
    ISSN: 0193-1857 , 1522-1547
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477329-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Gastrointestinal and Liver Physiology Vol. 292, No. 2 ( 2007-02), p. G620-G627
    In: American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 292, No. 2 ( 2007-02), p. G620-G627
    Abstract: Unlike the small intestine and colon where γ-radiation-induced apoptosis has previously been well characterized, the response of murine gastric epithelium to γ-radiation has not been investigated in detail. Apoptosis was therefore assessed on a cell positional basis in gastric antral and corpus glands from adult male mice following γ-radiation. Maximum numbers of apoptotic cells were observed in both antrum and corpus at 48 h and at radiation doses greater than 12 Gy. However, the number of apoptotic cells observed in the gastric epithelium was much lower than observed in the small intestine or colon after similar doses of radiation. Hematoxylin and eosin, caspase 3 immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling detected similar numbers and cell positional distributions of apoptotic cells, hence hematoxylin and eosin was used for subsequent studies. The highest numbers of apoptotic cells were observed at cell positions 5–6 in the antrum and cell positions 15–18 in the corpus. These distributions coincided with the distributions of PCNA-labeled proliferating cells, but not with the distributions of H + -K + -ATPase-labeled parietal cells or TFF2-labeled mucous neck cells. Decreased numbers of apoptotic gastric epithelial cells were observed in p53-null, bak-null, and bax-null mice compared with wild-type counterparts 6 and 48 h after 12 Gy γ-radiation. Significantly increased numbers of apoptotic gastric epithelial cells were observed in bcl-2-null mice compared with wild-type littermates 6 h after 12 Gy γ-radiation. Radiation therefore induces apoptosis in the proliferative zone of mouse gastric epithelium. This response is regulated by the expression of p53, bak, bax, and bcl-2.
    Type of Medium: Online Resource
    ISSN: 0193-1857 , 1522-1547
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477329-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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