Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans
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...
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| Veröffentlicht in: | Pathology 2005-02, Vol.37 (1), p.56-62 |
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| creator | Bowen, Joanne M. Gibson, Rachel J. Keefe, Dorothy M. Cummins, Adrian G. |
| description | 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. |
| doi_str_mv | 10.1080/00313020400023461 |
| format | Article |
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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.</description><identifier>ISSN: 0031-3025</identifier><identifier>EISSN: 1465-3931</identifier><identifier>DOI: 10.1080/00313020400023461</identifier><identifier>PMID: 15875735</identifier><language>eng</language><publisher>London: Informa UK Ltd</publisher><subject>Animals ; Antineoplastic Agents - therapeutic use ; Apoptosis - drug effects ; bcl-2 Homologous Antagonist-Killer Protein ; bcl-2-Associated X Protein ; Biological and medical sciences ; Caspase 3 ; Caspases - drug effects ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa - drug effects ; Intestinal Neoplasms - drug therapy ; Investigative techniques, diagnostic techniques (general aspects) ; Medical sciences ; Membrane Proteins - drug effects ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Proto-Oncogene Proteins c-bcl-2 - drug effects ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Tumor Suppressor Protein p53 - drug effects</subject><ispartof>Pathology, 2005-02, Vol.37 (1), p.56-62</ispartof><rights>2005 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 2005</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/00313020400023461$$EPDF$$P50$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/00313020400023461$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,61197,61378</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16511419$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15875735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bowen, Joanne M.</creatorcontrib><creatorcontrib>Gibson, Rachel J.</creatorcontrib><creatorcontrib>Keefe, Dorothy M.</creatorcontrib><creatorcontrib>Cummins, Adrian G.</creatorcontrib><title>Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans</title><title>Pathology</title><addtitle>Pathology</addtitle><description>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.</description><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2 Homologous Antagonist-Killer Protein</subject><subject>bcl-2-Associated X Protein</subject><subject>Biological and medical sciences</subject><subject>Caspase 3</subject><subject>Caspases - drug effects</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Intestinal Neoplasms - drug therapy</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Medical sciences</subject><subject>Membrane Proteins - drug effects</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Proto-Oncogene Proteins c-bcl-2 - drug effects</subject><subject>Rats</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Tumor Suppressor Protein p53 - drug effects</subject><issn>0031-3025</issn><issn>1465-3931</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpl0UtPwzAMAOAIgdgY_AAuKBeOhWR5NBUnmHhJk7jAuXKzZO1omypJJfbvydgQBy62LH-2ZBmhS0puKFHklhBGGZkTTgiZMy7pEZpSLkXGCkaP0XTXzxIQE3QWwiYprpQ6RRMqVC5yJqbILrbRRffVaKxr07lYGw_DFo-DN-uxhWgCHrzLYHBDgok9wBeGfpXyJ256nAZw6KBtU5FwbHqDncUeYvhh9dhBH87RiYU2mItDnqGPp8f3xUu2fHt-XdwvszWjecxkZZS2XBq-IoViFXBrGaG0MEClKaSoFHCjJSt4KhTjOQheaDA2T3Gl2Axd7fcOY9WZVTn4pgO_LX8PTuD6ACBoaK2HXjfhz0lBKadFcnd71_TW-Q5qA22sNXhTbtzo-3RESUm5e0P57w3sGyG5eMQ</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Bowen, Joanne M.</creator><creator>Gibson, Rachel J.</creator><creator>Keefe, Dorothy M.</creator><creator>Cummins, Adrian G.</creator><general>Informa UK Ltd</general><general>Taylor and Francis</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20050201</creationdate><title>Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans</title><author>Bowen, Joanne M. ; Gibson, Rachel J. ; Keefe, Dorothy M. ; Cummins, Adrian G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g317t-6be8cf46e4d0983ba4ff30119ea16e965b8a4ec63949658347a549caef79cad83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>bcl-2 Homologous Antagonist-Killer Protein</topic><topic>bcl-2-Associated X Protein</topic><topic>Biological and medical sciences</topic><topic>Caspase 3</topic><topic>Caspases - drug effects</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Intestinal Neoplasms - drug therapy</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Medical sciences</topic><topic>Membrane Proteins - drug effects</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Proto-Oncogene Proteins c-bcl-2 - drug effects</topic><topic>Rats</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Tumor Suppressor Protein p53 - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bowen, Joanne M.</creatorcontrib><creatorcontrib>Gibson, Rachel J.</creatorcontrib><creatorcontrib>Keefe, Dorothy M.</creatorcontrib><creatorcontrib>Cummins, Adrian G.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bowen, Joanne M.</au><au>Gibson, Rachel J.</au><au>Keefe, Dorothy M.</au><au>Cummins, Adrian G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans</atitle><jtitle>Pathology</jtitle><addtitle>Pathology</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>37</volume><issue>1</issue><spage>56</spage><epage>62</epage><pages>56-62</pages><issn>0031-3025</issn><eissn>1465-3931</eissn><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.</abstract><cop>London</cop><pub>Informa UK Ltd</pub><pmid>15875735</pmid><doi>10.1080/00313020400023461</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Taylor & Francis Journals Complete; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic Agents - therapeutic use Apoptosis - drug effects bcl-2 Homologous Antagonist-Killer Protein bcl-2-Associated X Protein Biological and medical sciences Caspase 3 Caspases - drug effects Female Humans Immunohistochemistry Intestinal Mucosa - drug effects Intestinal Neoplasms - drug therapy Investigative techniques, diagnostic techniques (general aspects) Medical sciences Membrane Proteins - drug effects Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Proto-Oncogene Proteins c-bcl-2 - drug effects Rats Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Tumor Suppressor Protein p53 - drug effects |
| title | Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans |
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