Novel application of amino-acid buffered solution for neuroprotection against ischemia/reperfusion injury
Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine-tryptophan-ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat...
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| Veröffentlicht in: | PloS one 2019-09, Vol.14 (9), p.e0221039-e0221039 |
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| creator | Hsu, Jiun Wang, Chih-Hsien Huang, Shu-Chien Chen, Yung-Wei Yu, Shengpin Hwang, Juey-Jen Lin, Jou-Wei Ma, Ming-Chieh Chen, Yih-Sharng |
| description | Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine-tryptophan-ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) expression were evaluated at different time points up to 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluation of NOX4 and H2O2 levels in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persistent HIF-1α expression and reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK's effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity, and NOX4 gene expression were all decreased in the brain specimens of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution by maintaining elevated HIF-1α level, which was associated with inhibited procaspase-3 activation and decreased NOX4 expression. |
| doi_str_mv | 10.1371/journal.pone.0221039 |
| format | Article |
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Histidine-tryptophan-ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) expression were evaluated at different time points up to 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluation of NOX4 and H2O2 levels in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persistent HIF-1α expression and reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK's effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity, and NOX4 gene expression were all decreased in the brain specimens of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution by maintaining elevated HIF-1α level, which was associated with inhibited procaspase-3 activation and decreased NOX4 expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0221039</identifier><identifier>PMID: 31504040</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Adenine ; Amino acids ; Amino Acids - chemistry ; Amino Acids - pharmacology ; Animals ; Apoptosis ; Asphyxia ; Asphyxia - complications ; Asphyxia - metabolism ; Biocompatibility ; Biology and Life Sciences ; Biomarkers ; Brain ; Brain damage ; Brain injury ; Buffers ; Cardiac arrest ; Cardiopulmonary resuscitation ; Care and treatment ; Carotid artery ; Caspase ; Caspase-3 ; Cerebral blood flow ; CPR ; Cytokines ; Cytotoxicity ; Disease Models, Animal ; Gene expression ; Genes ; Genetic aspects ; Heart surgery ; Histidine ; Hydrogen peroxide ; Hydrogen Peroxide - metabolism ; Hydrogen Peroxide - pharmacology ; Hypoxia ; Hypoxia - metabolism ; Hypoxia-inducible factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Hypoxia-inducible factors ; In vivo methods and tests ; Injuries ; Intensive care ; Ischemia ; Ketoglutaric acid ; Male ; Medicine ; Medicine and Health Sciences ; NAD(P)H oxidase ; NADPH Oxidase 4 - metabolism ; NADPH-diaphorase ; Neurons ; Neurons - drug effects ; Neurons - metabolism ; Neuroprotection ; Neuroprotection - drug effects ; Neuroprotective Agents - chemistry ; Neuroprotective Agents - pharmacology ; Niacinamide ; Nicotinamide ; Nicotinamide adenine dinucleotide ; NOX4 gene ; NOX4 protein ; Organ transplantation ; Oxidases ; Oxidative Stress ; Phosphates ; Physical Sciences ; Preservatives ; Purines ; Rats ; Reperfusion ; Reperfusion injury ; Reperfusion Injury - etiology ; Reperfusion Injury - metabolism ; Reperfusion Injury - prevention & control ; Resuscitation ; Surgery ; Time dependence ; Toxicity ; Transplantation ; Tryptophan</subject><ispartof>PloS one, 2019-09, Vol.14 (9), p.e0221039-e0221039</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Hsu 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>2019 Hsu et al 2019 Hsu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-3b0a122c0816be5538a16902251972b92ce3d4c19612ae4bd71c2ee9880c1de3</citedby><cites>FETCH-LOGICAL-c692t-3b0a122c0816be5538a16902251972b92ce3d4c19612ae4bd71c2ee9880c1de3</cites><orcidid>0000-0003-3846-8162</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/PMC6736298/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736298/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31504040$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsu, Jiun</creatorcontrib><creatorcontrib>Wang, Chih-Hsien</creatorcontrib><creatorcontrib>Huang, Shu-Chien</creatorcontrib><creatorcontrib>Chen, Yung-Wei</creatorcontrib><creatorcontrib>Yu, Shengpin</creatorcontrib><creatorcontrib>Hwang, Juey-Jen</creatorcontrib><creatorcontrib>Lin, Jou-Wei</creatorcontrib><creatorcontrib>Ma, Ming-Chieh</creatorcontrib><creatorcontrib>Chen, Yih-Sharng</creatorcontrib><title>Novel application of amino-acid buffered solution for neuroprotection against ischemia/reperfusion injury</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine-tryptophan-ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) expression were evaluated at different time points up to 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluation of NOX4 and H2O2 levels in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persistent HIF-1α expression and reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK's effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity, and NOX4 gene expression were all decreased in the brain specimens of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution by maintaining elevated HIF-1α level, which was associated with inhibited procaspase-3 activation and decreased NOX4 expression.</description><subject>Activation</subject><subject>Adenine</subject><subject>Amino acids</subject><subject>Amino Acids - chemistry</subject><subject>Amino Acids - pharmacology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Asphyxia</subject><subject>Asphyxia - complications</subject><subject>Asphyxia - metabolism</subject><subject>Biocompatibility</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Brain</subject><subject>Brain damage</subject><subject>Brain injury</subject><subject>Buffers</subject><subject>Cardiac arrest</subject><subject>Cardiopulmonary resuscitation</subject><subject>Care and treatment</subject><subject>Carotid artery</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cerebral blood flow</subject><subject>CPR</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Heart surgery</subject><subject>Histidine</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>Hypoxia-inducible factor 1</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Hypoxia-inducible factors</subject><subject>In vivo methods and tests</subject><subject>Injuries</subject><subject>Intensive care</subject><subject>Ischemia</subject><subject>Ketoglutaric acid</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>NAD(P)H oxidase</subject><subject>NADPH Oxidase 4 - metabolism</subject><subject>NADPH-diaphorase</subject><subject>Neurons</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neuroprotection</subject><subject>Neuroprotection - drug effects</subject><subject>Neuroprotective Agents - chemistry</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Niacinamide</subject><subject>Nicotinamide</subject><subject>Nicotinamide adenine dinucleotide</subject><subject>NOX4 gene</subject><subject>NOX4 protein</subject><subject>Organ transplantation</subject><subject>Oxidases</subject><subject>Oxidative Stress</subject><subject>Phosphates</subject><subject>Physical Sciences</subject><subject>Preservatives</subject><subject>Purines</subject><subject>Rats</subject><subject>Reperfusion</subject><subject>Reperfusion injury</subject><subject>Reperfusion Injury - etiology</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Resuscitation</subject><subject>Surgery</subject><subject>Time dependence</subject><subject>Toxicity</subject><subject>Transplantation</subject><subject>Tryptophan</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99r2zAQx83YWLtu_8HYDIOxPSTVD1u2XgaldFugrLCVvYqzfE4UFMuT7LL-91USp8SjD0MPNnef--rudJckbymZU17Q87UbfAt23rkW54QxSrh8lpxSydlMMMKfH_2fJK9CWBOS81KIl8kJpznJ4jlNzA93hzaFrrNGQ29cm7omhY1p3Qy0qdNqaBr0WKfB2WHnb5xPWxy867zrUe9ssATThj41Qa9wY-DcY4e-GcLWadr14O9fJy8asAHfjN-z5Pbr1e3l99n1zbfF5cX1TAvJ-hmvCFDGNCmpqDCPGQMVMtaXU1mwSjKNvM40lYIywKyqC6oZoixLommN_Cx5v5ftrAtqbFJQjJVlbEcUicRiT9QO1qrzZgP-XjkwamdwfqnA90ZbVHnWCFZrAYWssgIJ5KQWTVmXu8RIFbW-jLcN1QZrjW3vwU5Ep57WrNTS3SlRcMFkGQU-jQLe_Rkw9GoTe4jWQotu2OddMFJIFtEP_6BPVzdSS4gFmLZx8V69FVUXuZRxBkq-1Zo_QcVTx9fTcaIaE-2TgM-TgMj0-LdfwhCCWvz6-f_sze8p-_GIXSHYfnWYtDAFsz2ovQvBY_PYZErUdiEO3VDbhVDjQsSwd8cP9Bh02AD-AA6pBtw</recordid><startdate>20190910</startdate><enddate>20190910</enddate><creator>Hsu, Jiun</creator><creator>Wang, Chih-Hsien</creator><creator>Huang, Shu-Chien</creator><creator>Chen, Yung-Wei</creator><creator>Yu, Shengpin</creator><creator>Hwang, Juey-Jen</creator><creator>Lin, Jou-Wei</creator><creator>Ma, Ming-Chieh</creator><creator>Chen, Yih-Sharng</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>AEUYN</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3846-8162</orcidid></search><sort><creationdate>20190910</creationdate><title>Novel application of amino-acid buffered solution for neuroprotection against ischemia/reperfusion injury</title><author>Hsu, Jiun ; Wang, Chih-Hsien ; Huang, Shu-Chien ; Chen, Yung-Wei ; Yu, Shengpin ; Hwang, Juey-Jen ; Lin, Jou-Wei ; Ma, Ming-Chieh ; Chen, Yih-Sharng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-3b0a122c0816be5538a16902251972b92ce3d4c19612ae4bd71c2ee9880c1de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activation</topic><topic>Adenine</topic><topic>Amino acids</topic><topic>Amino Acids - 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etiology</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Resuscitation</topic><topic>Surgery</topic><topic>Time dependence</topic><topic>Toxicity</topic><topic>Transplantation</topic><topic>Tryptophan</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsu, Jiun</creatorcontrib><creatorcontrib>Wang, Chih-Hsien</creatorcontrib><creatorcontrib>Huang, Shu-Chien</creatorcontrib><creatorcontrib>Chen, Yung-Wei</creatorcontrib><creatorcontrib>Yu, Shengpin</creatorcontrib><creatorcontrib>Hwang, Juey-Jen</creatorcontrib><creatorcontrib>Lin, Jou-Wei</creatorcontrib><creatorcontrib>Ma, Ming-Chieh</creatorcontrib><creatorcontrib>Chen, Yih-Sharng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</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</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</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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 Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>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 Korea</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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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>Hsu, Jiun</au><au>Wang, Chih-Hsien</au><au>Huang, Shu-Chien</au><au>Chen, Yung-Wei</au><au>Yu, Shengpin</au><au>Hwang, Juey-Jen</au><au>Lin, Jou-Wei</au><au>Ma, Ming-Chieh</au><au>Chen, Yih-Sharng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel application of amino-acid buffered solution for neuroprotection against ischemia/reperfusion injury</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-09-10</date><risdate>2019</risdate><volume>14</volume><issue>9</issue><spage>e0221039</spage><epage>e0221039</epage><pages>e0221039-e0221039</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine-tryptophan-ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) expression were evaluated at different time points up to 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluation of NOX4 and H2O2 levels in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persistent HIF-1α expression and reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK's effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity, and NOX4 gene expression were all decreased in the brain specimens of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution by maintaining elevated HIF-1α level, which was associated with inhibited procaspase-3 activation and decreased NOX4 expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31504040</pmid><doi>10.1371/journal.pone.0221039</doi><tpages>e0221039</tpages><orcidid>https://orcid.org/0000-0003-3846-8162</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-09, Vol.14 (9), p.e0221039-e0221039 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2288193519 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Activation Adenine Amino acids Amino Acids - chemistry Amino Acids - pharmacology Animals Apoptosis Asphyxia Asphyxia - complications Asphyxia - metabolism Biocompatibility Biology and Life Sciences Biomarkers Brain Brain damage Brain injury Buffers Cardiac arrest Cardiopulmonary resuscitation Care and treatment Carotid artery Caspase Caspase-3 Cerebral blood flow CPR Cytokines Cytotoxicity Disease Models, Animal Gene expression Genes Genetic aspects Heart surgery Histidine Hydrogen peroxide Hydrogen Peroxide - metabolism Hydrogen Peroxide - pharmacology Hypoxia Hypoxia - metabolism Hypoxia-inducible factor 1 Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Hypoxia-inducible factors In vivo methods and tests Injuries Intensive care Ischemia Ketoglutaric acid Male Medicine Medicine and Health Sciences NAD(P)H oxidase NADPH Oxidase 4 - metabolism NADPH-diaphorase Neurons Neurons - drug effects Neurons - metabolism Neuroprotection Neuroprotection - drug effects Neuroprotective Agents - chemistry Neuroprotective Agents - pharmacology Niacinamide Nicotinamide Nicotinamide adenine dinucleotide NOX4 gene NOX4 protein Organ transplantation Oxidases Oxidative Stress Phosphates Physical Sciences Preservatives Purines Rats Reperfusion Reperfusion injury Reperfusion Injury - etiology Reperfusion Injury - metabolism Reperfusion Injury - prevention & control Resuscitation Surgery Time dependence Toxicity Transplantation Tryptophan |
| title | Novel application of amino-acid buffered solution for neuroprotection against ischemia/reperfusion injury |
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