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https://hdl.handle.net/2440/17444
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Type: | Journal article |
Title: | Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans |
Author: | Bowen, J. Gibson, R. Keefe, D. Cummins, A. |
Citation: | Pathology, 2005; 37(1):56-62 |
Publisher: | Taylor & Francis |
Issue Date: | 2005 |
ISSN: | 0031-3025 1465-3931 |
Statement of Responsibility: | Joanne M. Bowen; Rachel J. Gibson; Dorothy M. Keefe; Adrian G. Cummins |
Abstract: | Aims: Small intestinal crypt cells rapidly undergo apoptosis in response to cytotoxic drug treatment that results in gastrointestinal toxicity. The Bcl-2 family have been implicated in both positive and negative regulation of intestinal cell apoptosis. The aim of this study was to examine the effect of cytotoxic treatment on Bcl-2 protein expression in patients and rats with tumours. Methods: Four pro- and four anti-apoptotic members of the Bcl-2 family, caspase-3 and p53 were examined in small intestinal crypts before and after treatment in rats and humans. Immunohistochemistry identified changes in protein expression over time, while relative RT-PCR was used to investigate mRNA expression in rat small intestine. Results: Cytotoxic treatment increased p53 and caspase-3 which coincided with elevated levels of apoptosis. Bax and Bak protein and mRNA expression also significantly increased at 6 hours following treatment in rats. Bax and Bak protein increased at day 1 after treatment in humans. Anti-apoptotic Mcl-1 protein decreased within 24 hours. Other Bcl-2 family members showed only modest changes. Conclusion: Increased expression of Bax and Bak but not other Bcl-2 family members is associated with apoptosis in small intestinal crypts and may amplify the sensitivity and susceptibility of crypt cells to chemotherapy-induced enteropathy. |
Keywords: | Intestinal Mucosa Animals Humans Rats Intestinal Neoplasms Caspases Membrane Proteins Proto-Oncogene Proteins c-bcl-2 RNA, Messenger Antineoplastic Agents Immunohistochemistry Reverse Transcriptase Polymerase Chain Reaction Apoptosis Female Tumor Suppressor Protein p53 bcl-2 Homologous Antagonist-Killer Protein bcl-2-Associated X Protein Caspase 3 |
DOI: | 10.1080/00313020400023461 |
Published version: | http://dx.doi.org/10.1080/00313020400023461 |
Appears in Collections: | Aurora harvest 6 Medicine publications |
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