Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients
Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions...
Gespeichert in:
| Veröffentlicht in: | PloS one 2017-02, Vol.12 (2), p.e0172024-e0172024 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0172024 |
|---|---|
| container_issue | 2 |
| container_start_page | e0172024 |
| container_title | PloS one |
| container_volume | 12 |
| creator | Nucci, Laura A Santos, Sidnéia S Brunialti, Milena K C Sharma, Narendra Kumar Machado, Flavia R Assunção, Murillo de Azevedo, Luciano C P Salomao, Reinaldo |
| description | Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions and resulting cell functions and pathways that are disturbed in septic patients.
Blood samples were obtained from 16 patients with sepsis secondary to community acquired pneumonia at admission (D0), and after 7 days (D7, N = 10) of therapy. Samples were also collected from 8 healthy volunteers who were matched according to age and gender. Gene expression of 84 genes was performed by real-time polymerase chain reactions. Their expression was considered up- or down-regulated when the fold change was greater than 1.5 compared to the healthy volunteers. A p-value of ≤ 0.05 was considered significant.
Twenty-two genes were differently expressed in D0 samples; most of them were down-regulated. When gene expression was analyzed according to the outcomes, higher number of altered genes and a higher intensity in the disturbance was observed in non-survivor than in survivor patients. The canonical pathways altered in D0 samples included interferon and iNOS signaling; the role of JAK1, JAK2 and TYK2 in interferon signaling; mitochondrial dysfunction; and superoxide radical degradation pathways. When analyzed according to outcomes, different pathways were disturbed in surviving and non-surviving patients. Mitochondrial dysfunction, oxidative phosphorylation and superoxide radical degradation pathway were among the most altered in non-surviving patients.
Our data show changes in the expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and oxidative phosphorylation. Importantly, distinct patterns are clearly observed in surviving and non-surviving patients. Interferon signaling, marked by changes in JAK-STAT modulation, had prominent changes in both survivors and non-survivors, whereas the redox imbalance (iNOS signaling, oxidative phosphorylation and superoxide radical degradation) affecting mitochondrial functions was prominent in non-surviving patients. |
| doi_str_mv | 10.1371/journal.pone.0172024 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1866630243</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A481039841</galeid><doaj_id>oai_doaj_org_article_0a422ee41b1042538c3a923e0cec2f86</doaj_id><sourcerecordid>A481039841</sourcerecordid><originalsourceid>FETCH-LOGICAL-c725t-e393b390d45525b88304f55802c178b79a3fe837d17c52be5e962146cef3dc5e3</originalsourceid><addsrcrecordid>eNqNk91u1DAQhSMEoqXwBggsVUIgsYt_E-cGqSqFVqooKoVby3EmWVdZO9jeqn0GXhqn3VZd1IteREnG3xyPz3iK4jXBc8Iq8uncr4LTw3z0DuaYVBRT_qTYJjWjs5Ji9vTe91bxIsZzjAWTZfm82KKSSFrVcrv4e3A5BojReod8h3pwEFEDg3e9dT1KHqUFIOsSBG3SFDo7PkVGR6NbiB_R970vPw5n_tK2OgLSrkVLm7xZeNcGqwd0vZLsBaBx4WN-wtWQ__Nu1qEIY7IGjTkALsWXxbNODxFerd87xa-vB2f7h7Pjk29H-3vHM1NRkWbAatawGrdcCCoaKRnmnRASU0Mq2VS1Zh1IVrWkMoI2IKAuKeGlgY61RgDbKd7e6I6Dj2rtY1Qke1Oy7CLLxNEN0Xp9rsZglzpcKa-tug740CsdcukDKKw5pQCcNARzmg02TNeUATZgaCfLrPV5vduqWUJr8kmDHjZEN1ecXajeXyjBMM4dzALv1wLB_1lBTGppo4Fh0A78aqq7opJxhh-DlpXgnDOR0d3_0IeNWFO9zme1rvO5RDOJqj0uCWa15CRT8wcoPV2RpTX5fnY2xzcSPmwkZCbBZer1KkZ19PP08ezJ70323T12AXpIi-iH1XTh4ibIb0ATfIwBurt-EKym8bp1Q03jpdbjldPe3O_lXdLtPLF_RNogLA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1866630243</pqid></control><display><type>article</type><title>Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients</title><source>PLoS</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>EZB Electronic Journals Library</source><creator>Nucci, Laura A ; Santos, Sidnéia S ; Brunialti, Milena K C ; Sharma, Narendra Kumar ; Machado, Flavia R ; Assunção, Murillo ; de Azevedo, Luciano C P ; Salomao, Reinaldo</creator><contributor>Cunha-Neto, Edecio</contributor><creatorcontrib>Nucci, Laura A ; Santos, Sidnéia S ; Brunialti, Milena K C ; Sharma, Narendra Kumar ; Machado, Flavia R ; Assunção, Murillo ; de Azevedo, Luciano C P ; Salomao, Reinaldo ; Cunha-Neto, Edecio</creatorcontrib><description>Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions and resulting cell functions and pathways that are disturbed in septic patients.
Blood samples were obtained from 16 patients with sepsis secondary to community acquired pneumonia at admission (D0), and after 7 days (D7, N = 10) of therapy. Samples were also collected from 8 healthy volunteers who were matched according to age and gender. Gene expression of 84 genes was performed by real-time polymerase chain reactions. Their expression was considered up- or down-regulated when the fold change was greater than 1.5 compared to the healthy volunteers. A p-value of ≤ 0.05 was considered significant.
Twenty-two genes were differently expressed in D0 samples; most of them were down-regulated. When gene expression was analyzed according to the outcomes, higher number of altered genes and a higher intensity in the disturbance was observed in non-survivor than in survivor patients. The canonical pathways altered in D0 samples included interferon and iNOS signaling; the role of JAK1, JAK2 and TYK2 in interferon signaling; mitochondrial dysfunction; and superoxide radical degradation pathways. When analyzed according to outcomes, different pathways were disturbed in surviving and non-surviving patients. Mitochondrial dysfunction, oxidative phosphorylation and superoxide radical degradation pathway were among the most altered in non-surviving patients.
Our data show changes in the expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and oxidative phosphorylation. Importantly, distinct patterns are clearly observed in surviving and non-surviving patients. Interferon signaling, marked by changes in JAK-STAT modulation, had prominent changes in both survivors and non-survivors, whereas the redox imbalance (iNOS signaling, oxidative phosphorylation and superoxide radical degradation) affecting mitochondrial functions was prominent in non-surviving patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0172024</identifier><identifier>PMID: 28182798</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Analysis ; Biology and Life Sciences ; Biomarkers - metabolism ; Care and treatment ; Cascades ; Cytokines ; Degradation ; Female ; Gene expression ; Genes ; Humans ; Infections ; Interferon ; Janus kinase ; Janus Kinase 1 - genetics ; Janus Kinase 1 - metabolism ; Janus kinase 2 ; Janus Kinase 2 - genetics ; Janus Kinase 2 - metabolism ; Kinases ; Male ; Medicine and Health Sciences ; Metabolism ; Microorganisms ; Middle Aged ; Mitochondria ; NAD(P)H oxidase ; NADPH Oxidases - genetics ; NADPH Oxidases - metabolism ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; Nitric-oxide synthase ; Oxidase ; Oxidative metabolism ; Oxidative Phosphorylation ; Oxidative stress ; Patients ; Phosphorylation ; Physical Sciences ; Pneumoviridae ; Polymerase chain reaction ; Risk factors ; Sepsis ; Sepsis - diagnosis ; Sepsis - genetics ; Signal Transduction ; Signaling ; Superoxide ; Survival Analysis ; Toll-Like Receptors - genetics ; Toll-Like Receptors - metabolism ; TYK2 Kinase - genetics ; TYK2 Kinase - metabolism ; Tyk2 protein</subject><ispartof>PloS one, 2017-02, Vol.12 (2), p.e0172024-e0172024</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Nucci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Nucci et al 2017 Nucci et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-e393b390d45525b88304f55802c178b79a3fe837d17c52be5e962146cef3dc5e3</citedby><cites>FETCH-LOGICAL-c725t-e393b390d45525b88304f55802c178b79a3fe837d17c52be5e962146cef3dc5e3</cites><orcidid>0000-0003-1149-4598</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/PMC5300193/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300193/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28182798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cunha-Neto, Edecio</contributor><creatorcontrib>Nucci, Laura A</creatorcontrib><creatorcontrib>Santos, Sidnéia S</creatorcontrib><creatorcontrib>Brunialti, Milena K C</creatorcontrib><creatorcontrib>Sharma, Narendra Kumar</creatorcontrib><creatorcontrib>Machado, Flavia R</creatorcontrib><creatorcontrib>Assunção, Murillo</creatorcontrib><creatorcontrib>de Azevedo, Luciano C P</creatorcontrib><creatorcontrib>Salomao, Reinaldo</creatorcontrib><title>Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions and resulting cell functions and pathways that are disturbed in septic patients.
Blood samples were obtained from 16 patients with sepsis secondary to community acquired pneumonia at admission (D0), and after 7 days (D7, N = 10) of therapy. Samples were also collected from 8 healthy volunteers who were matched according to age and gender. Gene expression of 84 genes was performed by real-time polymerase chain reactions. Their expression was considered up- or down-regulated when the fold change was greater than 1.5 compared to the healthy volunteers. A p-value of ≤ 0.05 was considered significant.
Twenty-two genes were differently expressed in D0 samples; most of them were down-regulated. When gene expression was analyzed according to the outcomes, higher number of altered genes and a higher intensity in the disturbance was observed in non-survivor than in survivor patients. The canonical pathways altered in D0 samples included interferon and iNOS signaling; the role of JAK1, JAK2 and TYK2 in interferon signaling; mitochondrial dysfunction; and superoxide radical degradation pathways. When analyzed according to outcomes, different pathways were disturbed in surviving and non-surviving patients. Mitochondrial dysfunction, oxidative phosphorylation and superoxide radical degradation pathway were among the most altered in non-surviving patients.
Our data show changes in the expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and oxidative phosphorylation. Importantly, distinct patterns are clearly observed in surviving and non-surviving patients. Interferon signaling, marked by changes in JAK-STAT modulation, had prominent changes in both survivors and non-survivors, whereas the redox imbalance (iNOS signaling, oxidative phosphorylation and superoxide radical degradation) affecting mitochondrial functions was prominent in non-surviving patients.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers - metabolism</subject><subject>Care and treatment</subject><subject>Cascades</subject><subject>Cytokines</subject><subject>Degradation</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Humans</subject><subject>Infections</subject><subject>Interferon</subject><subject>Janus kinase</subject><subject>Janus Kinase 1 - genetics</subject><subject>Janus Kinase 1 - metabolism</subject><subject>Janus kinase 2</subject><subject>Janus Kinase 2 - genetics</subject><subject>Janus Kinase 2 - metabolism</subject><subject>Kinases</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Microorganisms</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>NAD(P)H oxidase</subject><subject>NADPH Oxidases - genetics</subject><subject>NADPH Oxidases - metabolism</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Nitric-oxide synthase</subject><subject>Oxidase</subject><subject>Oxidative metabolism</subject><subject>Oxidative Phosphorylation</subject><subject>Oxidative stress</subject><subject>Patients</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Pneumoviridae</subject><subject>Polymerase chain reaction</subject><subject>Risk factors</subject><subject>Sepsis</subject><subject>Sepsis - diagnosis</subject><subject>Sepsis - genetics</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Superoxide</subject><subject>Survival Analysis</subject><subject>Toll-Like Receptors - genetics</subject><subject>Toll-Like Receptors - metabolism</subject><subject>TYK2 Kinase - genetics</subject><subject>TYK2 Kinase - metabolism</subject><subject>Tyk2 protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk91u1DAQhSMEoqXwBggsVUIgsYt_E-cGqSqFVqooKoVby3EmWVdZO9jeqn0GXhqn3VZd1IteREnG3xyPz3iK4jXBc8Iq8uncr4LTw3z0DuaYVBRT_qTYJjWjs5Ji9vTe91bxIsZzjAWTZfm82KKSSFrVcrv4e3A5BojReod8h3pwEFEDg3e9dT1KHqUFIOsSBG3SFDo7PkVGR6NbiB_R970vPw5n_tK2OgLSrkVLm7xZeNcGqwd0vZLsBaBx4WN-wtWQ__Nu1qEIY7IGjTkALsWXxbNODxFerd87xa-vB2f7h7Pjk29H-3vHM1NRkWbAatawGrdcCCoaKRnmnRASU0Mq2VS1Zh1IVrWkMoI2IKAuKeGlgY61RgDbKd7e6I6Dj2rtY1Qke1Oy7CLLxNEN0Xp9rsZglzpcKa-tug740CsdcukDKKw5pQCcNARzmg02TNeUATZgaCfLrPV5vduqWUJr8kmDHjZEN1ecXajeXyjBMM4dzALv1wLB_1lBTGppo4Fh0A78aqq7opJxhh-DlpXgnDOR0d3_0IeNWFO9zme1rvO5RDOJqj0uCWa15CRT8wcoPV2RpTX5fnY2xzcSPmwkZCbBZer1KkZ19PP08ezJ70323T12AXpIi-iH1XTh4ibIb0ATfIwBurt-EKym8bp1Q03jpdbjldPe3O_lXdLtPLF_RNogLA</recordid><startdate>20170209</startdate><enddate>20170209</enddate><creator>Nucci, Laura A</creator><creator>Santos, Sidnéia S</creator><creator>Brunialti, Milena K C</creator><creator>Sharma, Narendra Kumar</creator><creator>Machado, Flavia R</creator><creator>Assunção, Murillo</creator><creator>de Azevedo, Luciano C P</creator><creator>Salomao, Reinaldo</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1149-4598</orcidid></search><sort><creationdate>20170209</creationdate><title>Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients</title><author>Nucci, Laura A ; Santos, Sidnéia S ; Brunialti, Milena K C ; Sharma, Narendra Kumar ; Machado, Flavia R ; Assunção, Murillo ; de Azevedo, Luciano C P ; Salomao, Reinaldo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-e393b390d45525b88304f55802c178b79a3fe837d17c52be5e962146cef3dc5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers - metabolism</topic><topic>Care and treatment</topic><topic>Cascades</topic><topic>Cytokines</topic><topic>Degradation</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Humans</topic><topic>Infections</topic><topic>Interferon</topic><topic>Janus kinase</topic><topic>Janus Kinase 1 - genetics</topic><topic>Janus Kinase 1 - metabolism</topic><topic>Janus kinase 2</topic><topic>Janus Kinase 2 - genetics</topic><topic>Janus Kinase 2 - metabolism</topic><topic>Kinases</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Microorganisms</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>NAD(P)H oxidase</topic><topic>NADPH Oxidases - genetics</topic><topic>NADPH Oxidases - metabolism</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Nitric-oxide synthase</topic><topic>Oxidase</topic><topic>Oxidative metabolism</topic><topic>Oxidative Phosphorylation</topic><topic>Oxidative stress</topic><topic>Patients</topic><topic>Phosphorylation</topic><topic>Physical Sciences</topic><topic>Pneumoviridae</topic><topic>Polymerase chain reaction</topic><topic>Risk factors</topic><topic>Sepsis</topic><topic>Sepsis - diagnosis</topic><topic>Sepsis - genetics</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Superoxide</topic><topic>Survival Analysis</topic><topic>Toll-Like Receptors - genetics</topic><topic>Toll-Like Receptors - metabolism</topic><topic>TYK2 Kinase - genetics</topic><topic>TYK2 Kinase - metabolism</topic><topic>Tyk2 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nucci, Laura A</creatorcontrib><creatorcontrib>Santos, Sidnéia S</creatorcontrib><creatorcontrib>Brunialti, Milena K C</creatorcontrib><creatorcontrib>Sharma, Narendra Kumar</creatorcontrib><creatorcontrib>Machado, Flavia R</creatorcontrib><creatorcontrib>Assunção, Murillo</creatorcontrib><creatorcontrib>de Azevedo, Luciano C P</creatorcontrib><creatorcontrib>Salomao, Reinaldo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints</collection><collection>Science (Gale in Context)</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Database (1962 - current)</collection><collection>ProQuest Agriculture & Environmental Science Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nucci, Laura A</au><au>Santos, Sidnéia S</au><au>Brunialti, Milena K C</au><au>Sharma, Narendra Kumar</au><au>Machado, Flavia R</au><au>Assunção, Murillo</au><au>de Azevedo, Luciano C P</au><au>Salomao, Reinaldo</au><au>Cunha-Neto, Edecio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-02-09</date><risdate>2017</risdate><volume>12</volume><issue>2</issue><spage>e0172024</spage><epage>e0172024</epage><pages>e0172024-e0172024</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions and resulting cell functions and pathways that are disturbed in septic patients.
Blood samples were obtained from 16 patients with sepsis secondary to community acquired pneumonia at admission (D0), and after 7 days (D7, N = 10) of therapy. Samples were also collected from 8 healthy volunteers who were matched according to age and gender. Gene expression of 84 genes was performed by real-time polymerase chain reactions. Their expression was considered up- or down-regulated when the fold change was greater than 1.5 compared to the healthy volunteers. A p-value of ≤ 0.05 was considered significant.
Twenty-two genes were differently expressed in D0 samples; most of them were down-regulated. When gene expression was analyzed according to the outcomes, higher number of altered genes and a higher intensity in the disturbance was observed in non-survivor than in survivor patients. The canonical pathways altered in D0 samples included interferon and iNOS signaling; the role of JAK1, JAK2 and TYK2 in interferon signaling; mitochondrial dysfunction; and superoxide radical degradation pathways. When analyzed according to outcomes, different pathways were disturbed in surviving and non-surviving patients. Mitochondrial dysfunction, oxidative phosphorylation and superoxide radical degradation pathway were among the most altered in non-surviving patients.
Our data show changes in the expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and oxidative phosphorylation. Importantly, distinct patterns are clearly observed in surviving and non-surviving patients. Interferon signaling, marked by changes in JAK-STAT modulation, had prominent changes in both survivors and non-survivors, whereas the redox imbalance (iNOS signaling, oxidative phosphorylation and superoxide radical degradation) affecting mitochondrial functions was prominent in non-surviving patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28182798</pmid><doi>10.1371/journal.pone.0172024</doi><tpages>e0172024</tpages><orcidid>https://orcid.org/0000-0003-1149-4598</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-02, Vol.12 (2), p.e0172024-e0172024 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1866630243 |
| source | PLoS; MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Aged Aged, 80 and over Analysis Biology and Life Sciences Biomarkers - metabolism Care and treatment Cascades Cytokines Degradation Female Gene expression Genes Humans Infections Interferon Janus kinase Janus Kinase 1 - genetics Janus Kinase 1 - metabolism Janus kinase 2 Janus Kinase 2 - genetics Janus Kinase 2 - metabolism Kinases Male Medicine and Health Sciences Metabolism Microorganisms Middle Aged Mitochondria NAD(P)H oxidase NADPH Oxidases - genetics NADPH Oxidases - metabolism Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism Nitric-oxide synthase Oxidase Oxidative metabolism Oxidative Phosphorylation Oxidative stress Patients Phosphorylation Physical Sciences Pneumoviridae Polymerase chain reaction Risk factors Sepsis Sepsis - diagnosis Sepsis - genetics Signal Transduction Signaling Superoxide Survival Analysis Toll-Like Receptors - genetics Toll-Like Receptors - metabolism TYK2 Kinase - genetics TYK2 Kinase - metabolism Tyk2 protein |
| title | Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T21%3A29%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20of%20genes%20belonging%20to%20the%20interacting%20TLR%20cascades,%20NADPH-oxidase%20and%20mitochondrial%20oxidative%20phosphorylation%20in%20septic%20patients&rft.jtitle=PloS%20one&rft.au=Nucci,%20Laura%20A&rft.date=2017-02-09&rft.volume=12&rft.issue=2&rft.spage=e0172024&rft.epage=e0172024&rft.pages=e0172024-e0172024&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0172024&rft_dat=%3Cgale_plos_%3EA481039841%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1866630243&rft_id=info:pmid/28182798&rft_galeid=A481039841&rft_doaj_id=oai_doaj_org_article_0a422ee41b1042538c3a923e0cec2f86&rfr_iscdi=true |