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Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria / Martin, Sheldon; Matthew, Turner

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Swansesa University Authors: Martin, Sheldon, Matthew, Turner

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DOI (Published version): 10.1101/679068

Abstract

Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient fo...

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Published: 2019
URI: https://cronfa.swan.ac.uk/Record/cronfa50982
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2019-09-26T16:38:40.4582049</datestamp><bib-version>v2</bib-version><id>50982</id><entry>2019-07-01</entry><title>Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria</title><swanseaauthors><author><sid>ab0f74b794e59cc270c69e63ee1d9748</sid><ORCID>0000-0001-7902-5558</ORCID><firstname>Martin</firstname><surname>Sheldon</surname><name>Martin Sheldon</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>d6ee69e43774ed1124d27923140b1e0b</sid><ORCID>0000-0002-1369-4051</ORCID><firstname>Matthew</firstname><surname>Turner</surname><name>Matthew Turner</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2019-07-01</date><deptcode>BMS</deptcode><abstract>Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine helped protect cells against cholesterol-dependent cytolysins because glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 &#xB1; 0.6 vs. 34.4 &#xB1; 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 &#xB1; 0.3 vs. 9.4 &#xB1; 1.0 AU). The cytoprotective effect of glutamine was not dependent on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria.</abstract><type>Journal Article</type><journal>bioRxiv</journal><publisher/><keywords/><publishedDay>21</publishedDay><publishedMonth>6</publishedMonth><publishedYear>2019</publishedYear><publishedDate>2019-06-21</publishedDate><doi>10.1101/679068</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><sponsorsfunders>BBSRC</sponsorsfunders><lastEdited>2019-09-26T16:38:40.4582049</lastEdited><Created>2019-07-01T12:00:49.5707095</Created><path><level id="1">Swansea University Medical School</level><level id="2">Medicine</level></path><authors><author><firstname>Matthew</firstname><surname>Turner</surname><orcid>0000-0002-1369-4051</orcid><order>1</order></author><author><firstname>Sian E</firstname><surname>Owens</surname><order>2</order></author><author><firstname>Martin</firstname><surname>Sheldon</surname><orcid>0000-0001-7902-5558</orcid><order>3</order></author></authors><documents><document><filename>0050982-01072019120508.pdf</filename><originalFilename>679068.full.pdf</originalFilename><uploaded>2019-07-01T12:05:08.1000000</uploaded><type>Output</type><contentLength>1636825</contentLength><contentType>application/pdf</contentType><version>Author's Original</version><cronfaStatus>true</cronfaStatus><action/><embargoDate>2019-07-01T00:00:00.0000000</embargoDate><documentNotes>Released under the terms of a Creative Commons Attribution License (CC-BY).</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents></rfc1807>
spelling 2019-09-26T16:38:40.4582049 v2 50982 2019-07-01 Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria ab0f74b794e59cc270c69e63ee1d9748 0000-0001-7902-5558 Martin Sheldon Martin Sheldon true false d6ee69e43774ed1124d27923140b1e0b 0000-0002-1369-4051 Matthew Turner Matthew Turner true false 2019-07-01 BMS Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine helped protect cells against cholesterol-dependent cytolysins because glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 ± 0.6 vs. 34.4 ± 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 ± 0.3 vs. 9.4 ± 1.0 AU). The cytoprotective effect of glutamine was not dependent on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria. Journal Article bioRxiv 21 6 2019 2019-06-21 10.1101/679068 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University BBSRC 2019-09-26T16:38:40.4582049 2019-07-01T12:00:49.5707095 Swansea University Medical School Medicine Matthew Turner 0000-0002-1369-4051 1 Sian E Owens 2 Martin Sheldon 0000-0001-7902-5558 3 0050982-01072019120508.pdf 679068.full.pdf 2019-07-01T12:05:08.1000000 Output 1636825 application/pdf Author's Original true 2019-07-01T00:00:00.0000000 Released under the terms of a Creative Commons Attribution License (CC-BY). true eng
title Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
spellingShingle Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
Martin, Sheldon
Matthew, Turner
title_short Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_full Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_fullStr Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_full_unstemmed Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_sort Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
author_id_str_mv ab0f74b794e59cc270c69e63ee1d9748
d6ee69e43774ed1124d27923140b1e0b
author_id_fullname_str_mv ab0f74b794e59cc270c69e63ee1d9748_***_Martin, Sheldon
d6ee69e43774ed1124d27923140b1e0b_***_Matthew, Turner
author Martin, Sheldon
Matthew, Turner
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publishDate 2019
institution Swansea University
doi_str_mv 10.1101/679068
college_str Swansea University Medical School
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hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
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description Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine helped protect cells against cholesterol-dependent cytolysins because glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 ± 0.6 vs. 34.4 ± 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 ± 0.3 vs. 9.4 ± 1.0 AU). The cytoprotective effect of glutamine was not dependent on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria.
published_date 2019-06-21T19:37:27Z
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