Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2
Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2
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DOI：
10.1152/ajpgi.00391.2006
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发表时间：
2007-02-01
影响因子：
4.5
通讯作者：
Pritchard, D. M.
中科院分区：
文献类型：
--
作者：
Przemeck, S. M. C.;Duckworth, C. A.;Pritchard, D. M.
与小肠和结肠中γ辐射诱导的细胞凋亡不同，小鼠胃上皮对γ辐射的反应尚未被详细研究。因此，在伽马辐射后，成年雄性小鼠胃窦腺和体腺的细胞位置基础上评估了细胞凋亡。在48 h和辐射剂量大于12 Gy时，胃窦和体部凋亡细胞数量最多。然而，在相同剂量的辐射后，胃上皮中凋亡细胞的数量远低于小肠或结肠。苏木精和伊红、caspase 3免疫组织化学和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口端标记检测到凋亡细胞的数量和细胞位置分布相似，因此使用苏木精和伊红进行后续研究。凋亡细胞数量最多的是在胃窦的5 ~ 6号细胞位置和体的15 ~ 18号细胞位置。这些分布与PCNA标记的增殖细胞的分布一致，但与H+- K+- atpasel标记的壁细胞或TFF2标记的黏液颈细胞的分布不一致。在12 Gy γ辐射后6和48小时，与野生型小鼠相比，p53-null、bak-null和bax-null小鼠的胃上皮细胞凋亡数量减少。12 Gy γ辐射后6 h， bcl- 2null小鼠胃上皮细胞凋亡数量明显高于野生型小鼠。因此，辐射可诱导小鼠胃上皮增殖带的细胞凋亡。这种反应受p53、bak、bax和bcl- 2的表达调控。
Unlike the small intestine and colon where gamma- radiation- induced apoptosis has previously been well characterized, the response of murine gastric epithelium to gamma- 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 gamma- 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+- ATPaselabeled 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 gamma-radiation. Significantly increased numbers of apoptotic gastric epithelial cells were observed in bcl- 2null mice compared with wild- type littermates 6 h after 12 Gy gamma-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.