Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2

Przemeck, S.M.C.; Duckworth, Carrie A.; Pritchard, D. Mark

doi:10.1152/ajpgi.00391.2006

Cited by 27 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Animals were whole-body ␥-irradiated by use of a Cs 137 source delivering a dose of 2.6 Gy/min. The dose and time course of ␥-irradiation was different for each tissue because susceptibility of induction of apoptosis is tissue specific and was determined from previous studies (8,19,22). For small intestine and colon, 1-Gy ␥-radiation was administered and mice were euthanized 4.5 h afterward.…”

Section: Methodsmentioning

confidence: 99%

“…This is therefore thought to represent a good animal model of H. pylori-induced gastric carcinogenesis in humans (10). Because female C57BL/6 are more susceptible to the effects of H. felis infection than males (7), we have investigated whether CD24 deletion affects the early stages of H. felis-induced gastric pathology using female mice and have conducted ␥-irradiation experiments with male mice since no sex difference has previously been reported with use of this stimulus (22).…”

mentioning

confidence: 99%

See 1 more Smart Citation

CD24 is expressed in gastric parietal cells and regulates apoptosis and the response toHelicobacter felisinfection in the murine stomach

Duckworth

Clyde

Pritchard

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

View full text Add to dashboard Cite

CD24 is expressed in the putative stem cells within several tissues and is overexpressed in gastric and colonic adenocarcinomas. Perturbed CD24 expression may therefore alter the response of gastrointestinal epithelia to damage-inducing stimuli that induce cancer. We have investigated the effects of CD24 deletion on gastric responses to Helicobacter felis infection and γ-irradiation using CD24-null mice. Gastric CD24 expression was determined by immunohistochemistry in C57BL/6 mice. Female CD24-null and C57BL/6 mice were infected with H. felis for 6 wk, and inflammation, proliferation, apoptosis, and parietal cell numbers were assessed in gastric tissue sections. Apoptosis and proliferation were analyzed on a cell-positional basis in stomach, small intestine, and colon of CD24-null and C57BL/6 mice following γ-irradiation. Apoptosis was also assessed in HT29 cells following CD24 siRNA transfection. Of CD24-positive cells in the gastric corpus, 98% were H(+)-K(+)-ATPase-expressing parietal cells. CD24-null mice showed more prominent gastric H. felis colonization than C57BL/6 mice but displayed a marked reduction in corpus inflammation, reduced Ki67 labeling, and less gastric atrophy 6 wk following infection. Corpus apoptosis was elevated in CD24-null mice, but this did not increase further with H. felis infection as observed in C57BL/6 mice. More apoptotic cells were found following γ-irradiation in the stomach, small intestine, and colon of CD24-null mice and following CD24 knockdown in vitro. In conclusion, CD24 is expressed in gastric parietal cells, where it modulates gastric responses to H. felis and γ-radiation. CD24 also regulates susceptibility to apoptosis in the distal murine gastrointestinal tract.

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

CD24 is expressed in gastric parietal cells and regulates apoptosis and the response toHelicobacter felisinfection in the murine stomach

Duckworth

Clyde

Pritchard

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

View full text Add to dashboard Cite

show abstract

“…Half-crypts (50/mouse) were assessed for the presence of goblet cells on a cell positional basis. Briefly, each cell position of 50 separate half-crypts was recorded as to whether it contained a goblet cell or a nongoblet cell, and the data were analyzed and presented in a manner identical to that previously published for the assessment of apoptotic cells in the intestinal epithelium (21,26). Data are presented as the mean number of goblet cells in 50 halfcrypts for a group of six mice or as plots of goblet cell index percentage against cell position along the crypt.…”

Section: Rna Extraction and Quantitative Rt-pcr Analysismentioning

confidence: 99%

KLF4 gene expression is inhibited by the notch signaling pathway that controls goblet cell differentiation in mouse gastrointestinal tract

Zheng¹,

Pritchard²,

Yang³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

In Kruppel-like factor (KLF)-4-deficient mice, colonic goblet cell numbers are significantly reduced. Goblet cell development is regulated by the Notch signaling pathway. The aim of this study was to examine whether Notch represses KLF4 expression to regulate goblet cell differentiation. We first detected that KLF4 gene expression was upregulated in a human progastrin-overexpressing mouse model where goblet cell hyperplasia has been observed. We then found that mice treated with a γ-secretase inhibitor (compound E, 10 μmol/kg) for 24 h, which inhibits the Notch signaling pathway, had significantly increased KLF4 mRNA levels in small intestine and colon, accompanied by an increased number of KLF4-expressing cells at the bottom of crypts in small intestine and colon. In a colon cancer cell line (HCT116 cells), KLF4 promoter activity was inhibited by a constitutively active form of Notch1 (ICN1) by transient cotransfection assays. This inhibition was significantly compromised by a dominant-negative RBPjk, a repressive mediator of the Notch signaling pathway. An ICN1-responsive element was then mapped in the human KLF4 promoter between −151 and −122 nucleotides upstream of the transcriptional start site. It was also found that an intact ICN1-responsive element is required for ICN1 to inhibit KLF4 promoter activity by transient cotransfection assays. Our findings thus reveal a possible mechanism by which KLF4 is inhibited by Notch, which controls goblet cell differentiation in mouse gastrointestinal tract.

show abstract

“…Bcl2 maintains mitochondrial outer membrane integrity (Teijido and Dejean ;Luo, Budihardjo et al 1998;Zhang, Holzgreve et al 2001). Bax can be activated by pro apoptotic stimuli or p53 and expression can be altered following radiation and is associated with resistance to chemotherapy (Miguel, Wajsenzon et al 2007), (Przemeck, Duckworth et al 2007), (Murphy, Mabruk et al 2002), (Johnson, Xiang et al 1998;Butt, Firth et al 2000), (Strobel, Swanson et al 1997), (Khanna, Wie et al 1996). This is in contrast to overexpression of bcl2 is associated with chemotherapy resistance and protects cells from radiation induced apoptosis (Hahn, Lai et al 2003), (Vrana, Grant et al 1999).…”

Section: Mitochondrial Proteins Bcl2/baxmentioning

confidence: 99%

Tumor Markers of Neo-Adjuvant Chemo-Radiation Response in Rectal Cancer

O’Sullivan¹,

Cathcart²,

Reynolds³

2011

Rectal Cancer - A Multidisciplinary Approach to Management

View full text Add to dashboard Cite

Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2

Abstract: Przemeck SM, Duckworth CA, Pritchard DM. Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2.

Cited by 27 publications

References 24 publications

CD24 is expressed in gastric parietal cells and regulates apoptosis and the response toHelicobacter felisinfection in the murine stomach

CD24 is expressed in gastric parietal cells and regulates apoptosis and the response toHelicobacter felisinfection in the murine stomach

KLF4 gene expression is inhibited by the notch signaling pathway that controls goblet cell differentiation in mouse gastrointestinal tract

Tumor Markers of Neo-Adjuvant Chemo-Radiation Response in Rectal Cancer

Contact Info

Product

Resources

About