Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage
Background and Purpose Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti‐cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and reg...
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| Veröffentlicht in: | British journal of pharmacology 2020-02, Vol.177 (3), p.687-700 |
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| container_title | British journal of pharmacology |
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| creator | Zeng, Huihong Li, Huan Yue, Mengzhen Fan, Ying Cheng, Jiaoqi Wu, Xincheng Xu, Rui Yang, Wuping Li, Manjun Tang, Jiahui Chen, Hongping Kuang, Bohai Fan, Guangqin Zhu, Qingxian Shao, Lijian |
| description | Background and Purpose
Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti‐cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and regeneration of intestinal stem cells. Here we have investigated the effects of isoprenaline on the damaged intestinal stem cells induced by chemotherapeutic treatments in mice.
Experimental Approach
The effects of inhibiting sympathetic and parasympathetic nerves on intestinal stem cells were examined in male C57BL/6J mice. Protection by isoprenaline of intestinal stem cells was assessed in the presence or absence of 5‐fluorouracil (5FU) or cisplatin. Cellular apoptosis, cell cycle, PI3K/Akt signalling, and NF‐κB signalling in intestinal stem cells were mechanistically evaluated.
Key Results
The sympathetic nerve inhibitor 6‐OHDA decreased the number and function of intestinal stem cells. 5FU or cisplatin treatment damaged both intestinal stem cells and sympathetic nerves. Notably, isoprenaline accelerated the recovery of intestinal stem cells after 5FU or cisplatin treatment. This protective effect of isoprenaline on damaged intestinal stem cells was mediated by β2‐adrenoceptors. The benefits of isoprenaline were mainly mediated by inhibiting cellular apoptosis induced by 5FU treatment, which might contribute to fine‐tuning regulating NF‐κB signalling pathway by isoprenaline administration.
Conclusions and Implications
Treatment with isoprenaline is a new approach to ameliorate the damage to intestinal stem cells following exposure to cancer chemotherapeutic agents. |
| doi_str_mv | 10.1111/bph.14883 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7012967</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2353313904</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4433-c62a4e95c21f862c0ea81b163ad14d62e853566e6961e3c5ecbda45ce99fdf773</originalsourceid><addsrcrecordid>eNp1kLFOwzAQhi0EoqUw8AIoEhNDWjt2HGdBggpopQoYYLZc59KmSuJgp6BuPALPyJPg0lLBgBdbvk_f3f0InRLcJ_4Mps28T5gQdA91CUt4GFNB9lEXY5yEhAjRQUfOLTD2xSQ-RB1KOBOe6aL7sTONhVqVRQ1BY00LunVBUbfg2sJ_B66FKtBQli7IrfHPOVSmnYNVzerz_aOos6WGLMhUpWZwjA5yVTo42d499Hx78zQchZOHu_HwahJqxigNNY8UgzTWEckFjzQGJciUcKoywjIegYhpzDnwlBOgOgY9zRSLNaRpnuVJQnvocuNtltMKMg11a1UpG1tUyq6kUYX8W6mLuZyZV5lgEqV8LTjfCqx5Wfpd5cIsrd_XyYjGlBKaYuapiw2lrXHOQr7rQLBcRy999PI7es-e_R5pR_5k7YHBBngrSlj9b5LXj6ON8gtUlZC8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2353313904</pqid></control><display><type>article</type><title>Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Zeng, Huihong ; Li, Huan ; Yue, Mengzhen ; Fan, Ying ; Cheng, Jiaoqi ; Wu, Xincheng ; Xu, Rui ; Yang, Wuping ; Li, Manjun ; Tang, Jiahui ; Chen, Hongping ; Kuang, Bohai ; Fan, Guangqin ; Zhu, Qingxian ; Shao, Lijian</creator><creatorcontrib>Zeng, Huihong ; Li, Huan ; Yue, Mengzhen ; Fan, Ying ; Cheng, Jiaoqi ; Wu, Xincheng ; Xu, Rui ; Yang, Wuping ; Li, Manjun ; Tang, Jiahui ; Chen, Hongping ; Kuang, Bohai ; Fan, Guangqin ; Zhu, Qingxian ; Shao, Lijian</creatorcontrib><description>Background and Purpose
Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti‐cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and regeneration of intestinal stem cells. Here we have investigated the effects of isoprenaline on the damaged intestinal stem cells induced by chemotherapeutic treatments in mice.
Experimental Approach
The effects of inhibiting sympathetic and parasympathetic nerves on intestinal stem cells were examined in male C57BL/6J mice. Protection by isoprenaline of intestinal stem cells was assessed in the presence or absence of 5‐fluorouracil (5FU) or cisplatin. Cellular apoptosis, cell cycle, PI3K/Akt signalling, and NF‐κB signalling in intestinal stem cells were mechanistically evaluated.
Key Results
The sympathetic nerve inhibitor 6‐OHDA decreased the number and function of intestinal stem cells. 5FU or cisplatin treatment damaged both intestinal stem cells and sympathetic nerves. Notably, isoprenaline accelerated the recovery of intestinal stem cells after 5FU or cisplatin treatment. This protective effect of isoprenaline on damaged intestinal stem cells was mediated by β2‐adrenoceptors. The benefits of isoprenaline were mainly mediated by inhibiting cellular apoptosis induced by 5FU treatment, which might contribute to fine‐tuning regulating NF‐κB signalling pathway by isoprenaline administration.
Conclusions and Implications
Treatment with isoprenaline is a new approach to ameliorate the damage to intestinal stem cells following exposure to cancer chemotherapeutic agents.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/bph.14883</identifier><identifier>PMID: 31648381</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>1-Phosphatidylinositol 3-kinase ; 5-Fluorouracil ; AKT protein ; Animals ; Antineoplastic Agents - toxicity ; Apoptosis ; Cell cycle ; Cell proliferation ; Chemotherapy ; Cisplatin ; Enteric nervous system ; Epithelial cells ; Intestinal Mucosa ; Intestine ; Isoproterenol - pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mucosa ; Parasympathetic nervous system ; Phosphatidylinositol 3-Kinases ; Regeneration ; Research Paper ; Research Papers ; Signal transduction ; Stem cell transplantation ; Stem Cells ; Sympathetic nerves</subject><ispartof>British journal of pharmacology, 2020-02, Vol.177 (3), p.687-700</ispartof><rights>2019 The British Pharmacological Society</rights><rights>2019 The British Pharmacological Society.</rights><rights>2020 The British Pharmacological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4433-c62a4e95c21f862c0ea81b163ad14d62e853566e6961e3c5ecbda45ce99fdf773</citedby><cites>FETCH-LOGICAL-c4433-c62a4e95c21f862c0ea81b163ad14d62e853566e6961e3c5ecbda45ce99fdf773</cites><orcidid>0000-0002-7000-7094</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012967/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012967/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31648381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zeng, Huihong</creatorcontrib><creatorcontrib>Li, Huan</creatorcontrib><creatorcontrib>Yue, Mengzhen</creatorcontrib><creatorcontrib>Fan, Ying</creatorcontrib><creatorcontrib>Cheng, Jiaoqi</creatorcontrib><creatorcontrib>Wu, Xincheng</creatorcontrib><creatorcontrib>Xu, Rui</creatorcontrib><creatorcontrib>Yang, Wuping</creatorcontrib><creatorcontrib>Li, Manjun</creatorcontrib><creatorcontrib>Tang, Jiahui</creatorcontrib><creatorcontrib>Chen, Hongping</creatorcontrib><creatorcontrib>Kuang, Bohai</creatorcontrib><creatorcontrib>Fan, Guangqin</creatorcontrib><creatorcontrib>Zhu, Qingxian</creatorcontrib><creatorcontrib>Shao, Lijian</creatorcontrib><title>Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Background and Purpose
Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti‐cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and regeneration of intestinal stem cells. Here we have investigated the effects of isoprenaline on the damaged intestinal stem cells induced by chemotherapeutic treatments in mice.
Experimental Approach
The effects of inhibiting sympathetic and parasympathetic nerves on intestinal stem cells were examined in male C57BL/6J mice. Protection by isoprenaline of intestinal stem cells was assessed in the presence or absence of 5‐fluorouracil (5FU) or cisplatin. Cellular apoptosis, cell cycle, PI3K/Akt signalling, and NF‐κB signalling in intestinal stem cells were mechanistically evaluated.
Key Results
The sympathetic nerve inhibitor 6‐OHDA decreased the number and function of intestinal stem cells. 5FU or cisplatin treatment damaged both intestinal stem cells and sympathetic nerves. Notably, isoprenaline accelerated the recovery of intestinal stem cells after 5FU or cisplatin treatment. This protective effect of isoprenaline on damaged intestinal stem cells was mediated by β2‐adrenoceptors. The benefits of isoprenaline were mainly mediated by inhibiting cellular apoptosis induced by 5FU treatment, which might contribute to fine‐tuning regulating NF‐κB signalling pathway by isoprenaline administration.
Conclusions and Implications
Treatment with isoprenaline is a new approach to ameliorate the damage to intestinal stem cells following exposure to cancer chemotherapeutic agents.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>5-Fluorouracil</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Antineoplastic Agents - toxicity</subject><subject>Apoptosis</subject><subject>Cell cycle</subject><subject>Cell proliferation</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Enteric nervous system</subject><subject>Epithelial cells</subject><subject>Intestinal Mucosa</subject><subject>Intestine</subject><subject>Isoproterenol - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mucosa</subject><subject>Parasympathetic nervous system</subject><subject>Phosphatidylinositol 3-Kinases</subject><subject>Regeneration</subject><subject>Research Paper</subject><subject>Research Papers</subject><subject>Signal transduction</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Sympathetic nerves</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLFOwzAQhi0EoqUw8AIoEhNDWjt2HGdBggpopQoYYLZc59KmSuJgp6BuPALPyJPg0lLBgBdbvk_f3f0InRLcJ_4Mps28T5gQdA91CUt4GFNB9lEXY5yEhAjRQUfOLTD2xSQ-RB1KOBOe6aL7sTONhVqVRQ1BY00LunVBUbfg2sJ_B66FKtBQli7IrfHPOVSmnYNVzerz_aOos6WGLMhUpWZwjA5yVTo42d499Hx78zQchZOHu_HwahJqxigNNY8UgzTWEckFjzQGJciUcKoywjIegYhpzDnwlBOgOgY9zRSLNaRpnuVJQnvocuNtltMKMg11a1UpG1tUyq6kUYX8W6mLuZyZV5lgEqV8LTjfCqx5Wfpd5cIsrd_XyYjGlBKaYuapiw2lrXHOQr7rQLBcRy999PI7es-e_R5pR_5k7YHBBngrSlj9b5LXj6ON8gtUlZC8</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Zeng, Huihong</creator><creator>Li, Huan</creator><creator>Yue, Mengzhen</creator><creator>Fan, Ying</creator><creator>Cheng, Jiaoqi</creator><creator>Wu, Xincheng</creator><creator>Xu, Rui</creator><creator>Yang, Wuping</creator><creator>Li, Manjun</creator><creator>Tang, Jiahui</creator><creator>Chen, Hongping</creator><creator>Kuang, Bohai</creator><creator>Fan, Guangqin</creator><creator>Zhu, Qingxian</creator><creator>Shao, Lijian</creator><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7000-7094</orcidid></search><sort><creationdate>202002</creationdate><title>Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage</title><author>Zeng, Huihong ; Li, Huan ; Yue, Mengzhen ; Fan, Ying ; Cheng, Jiaoqi ; Wu, Xincheng ; Xu, Rui ; Yang, Wuping ; Li, Manjun ; Tang, Jiahui ; Chen, Hongping ; Kuang, Bohai ; Fan, Guangqin ; Zhu, Qingxian ; Shao, Lijian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4433-c62a4e95c21f862c0ea81b163ad14d62e853566e6961e3c5ecbda45ce99fdf773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>5-Fluorouracil</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Antineoplastic Agents - toxicity</topic><topic>Apoptosis</topic><topic>Cell cycle</topic><topic>Cell proliferation</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Enteric nervous system</topic><topic>Epithelial cells</topic><topic>Intestinal Mucosa</topic><topic>Intestine</topic><topic>Isoproterenol - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mucosa</topic><topic>Parasympathetic nervous system</topic><topic>Phosphatidylinositol 3-Kinases</topic><topic>Regeneration</topic><topic>Research Paper</topic><topic>Research Papers</topic><topic>Signal transduction</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>Sympathetic nerves</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeng, Huihong</creatorcontrib><creatorcontrib>Li, Huan</creatorcontrib><creatorcontrib>Yue, Mengzhen</creatorcontrib><creatorcontrib>Fan, Ying</creatorcontrib><creatorcontrib>Cheng, Jiaoqi</creatorcontrib><creatorcontrib>Wu, Xincheng</creatorcontrib><creatorcontrib>Xu, Rui</creatorcontrib><creatorcontrib>Yang, Wuping</creatorcontrib><creatorcontrib>Li, Manjun</creatorcontrib><creatorcontrib>Tang, Jiahui</creatorcontrib><creatorcontrib>Chen, Hongping</creatorcontrib><creatorcontrib>Kuang, Bohai</creatorcontrib><creatorcontrib>Fan, Guangqin</creatorcontrib><creatorcontrib>Zhu, Qingxian</creatorcontrib><creatorcontrib>Shao, Lijian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeng, Huihong</au><au>Li, Huan</au><au>Yue, Mengzhen</au><au>Fan, Ying</au><au>Cheng, Jiaoqi</au><au>Wu, Xincheng</au><au>Xu, Rui</au><au>Yang, Wuping</au><au>Li, Manjun</au><au>Tang, Jiahui</au><au>Chen, Hongping</au><au>Kuang, Bohai</au><au>Fan, Guangqin</au><au>Zhu, Qingxian</au><au>Shao, Lijian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2020-02</date><risdate>2020</risdate><volume>177</volume><issue>3</issue><spage>687</spage><epage>700</epage><pages>687-700</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>Background and Purpose
Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti‐cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and regeneration of intestinal stem cells. Here we have investigated the effects of isoprenaline on the damaged intestinal stem cells induced by chemotherapeutic treatments in mice.
Experimental Approach
The effects of inhibiting sympathetic and parasympathetic nerves on intestinal stem cells were examined in male C57BL/6J mice. Protection by isoprenaline of intestinal stem cells was assessed in the presence or absence of 5‐fluorouracil (5FU) or cisplatin. Cellular apoptosis, cell cycle, PI3K/Akt signalling, and NF‐κB signalling in intestinal stem cells were mechanistically evaluated.
Key Results
The sympathetic nerve inhibitor 6‐OHDA decreased the number and function of intestinal stem cells. 5FU or cisplatin treatment damaged both intestinal stem cells and sympathetic nerves. Notably, isoprenaline accelerated the recovery of intestinal stem cells after 5FU or cisplatin treatment. This protective effect of isoprenaline on damaged intestinal stem cells was mediated by β2‐adrenoceptors. The benefits of isoprenaline were mainly mediated by inhibiting cellular apoptosis induced by 5FU treatment, which might contribute to fine‐tuning regulating NF‐κB signalling pathway by isoprenaline administration.
Conclusions and Implications
Treatment with isoprenaline is a new approach to ameliorate the damage to intestinal stem cells following exposure to cancer chemotherapeutic agents.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>31648381</pmid><doi>10.1111/bph.14883</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-7000-7094</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase 5-Fluorouracil AKT protein Animals Antineoplastic Agents - toxicity Apoptosis Cell cycle Cell proliferation Chemotherapy Cisplatin Enteric nervous system Epithelial cells Intestinal Mucosa Intestine Isoproterenol - pharmacology Male Mice Mice, Inbred C57BL Mucosa Parasympathetic nervous system Phosphatidylinositol 3-Kinases Regeneration Research Paper Research Papers Signal transduction Stem cell transplantation Stem Cells Sympathetic nerves |
| title | Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage |
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