Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats
Identifieur interne : 000516 ( Pmc/Curation ); précédent : 000515; suivant : 000517Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats
Auteurs : Lifang Chen [République populaire de Chine] ; Qiaohuan Tian [République populaire de Chine] ; Weihua Wang [République populaire de Chine]Source :
- Experimental and Therapeutic Medicine [ 1792-0981 ] ; 2019.
Abstract
The role of cold inducible RNA-binding protein (CIRP) in mediating ischemic brain injury in neonatal rats under chronic hypobaric hypoxia was investigated. The neonatal rat model of chronic hypobaric hypoxia and the cell culture model of SH-SY5Y cells exposed to hypoxia (1% O2) were constructed. The expression of CIRP and hypoxia-inducible factor-1α (HIF-1α) was detected after hypoxic exposure, and the apoptosis-related proteins were analyzed via terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and western blot analysis to detect neuronal apoptosis. Moreover, the effects of CIRP overexpression on HIF-1α and neuronal apoptosis were identified. Chronic hypobaric hypoxia can lead to HIF-1α expression and neuronal apoptosis in the body. CIRP was induced at early exposure (3 d/7 d). However, the CIRP level in the hypoxic group was obviously lower than that in the control group with the prolongation of exposure time (21 d). In addition, the knockdown of HIF-1α significantly reduced the neuronal apoptosis under hypoxic conditions, indicating that HIF-1α may promote apoptosis during exposure. The overexpression of CIRP significantly inhibited the upregulation of HIF-1α during hypoxia and the HIF-1α-mediated neuronal apoptosis. Results of the current study showed that, CIRP is involved in the ischemic brain injury induced by chronic hypoxia through downregulation of HIF-1α expression.
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DOI: 10.3892/etm.2019.7767
PubMed: 31410103
PubMed Central: 6676150
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats</title><author><name sortKey="Chen, Lifang" sort="Chen, Lifang" uniqKey="Chen L" first="Lifang" last="Chen">Lifang Chen</name><affiliation wicri:level="1"><nlm:aff id="af1-etm-0-0-7767">Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000</wicri:regionArea></affiliation></author><author><name sortKey="Tian, Qiaohuan" sort="Tian, Qiaohuan" uniqKey="Tian Q" first="Qiaohuan" last="Tian">Qiaohuan Tian</name><affiliation wicri:level="1"><nlm:aff id="af1-etm-0-0-7767">Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weihua" sort="Wang, Weihua" uniqKey="Wang W" first="Weihua" last="Wang">Weihua Wang</name><affiliation wicri:level="1"><nlm:aff id="af2-etm-0-0-7767">Department of Paediatrics, The First People's Hospital of Xianyang City, Xianyang, Shaanxi 712000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Paediatrics, The First People's Hospital of Xianyang City, Xianyang, Shaanxi 712000</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31410103</idno><idno type="pmc">6676150</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676150</idno><idno type="RBID">PMC:6676150</idno><idno type="doi">10.3892/etm.2019.7767</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000516</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000516</idno><idno type="wicri:Area/Pmc/Curation">000516</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000516</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats</title><author><name sortKey="Chen, Lifang" sort="Chen, Lifang" uniqKey="Chen L" first="Lifang" last="Chen">Lifang Chen</name><affiliation wicri:level="1"><nlm:aff id="af1-etm-0-0-7767">Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000</wicri:regionArea></affiliation></author><author><name sortKey="Tian, Qiaohuan" sort="Tian, Qiaohuan" uniqKey="Tian Q" first="Qiaohuan" last="Tian">Qiaohuan Tian</name><affiliation wicri:level="1"><nlm:aff id="af1-etm-0-0-7767">Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weihua" sort="Wang, Weihua" uniqKey="Wang W" first="Weihua" last="Wang">Weihua Wang</name><affiliation wicri:level="1"><nlm:aff id="af2-etm-0-0-7767">Department of Paediatrics, The First People's Hospital of Xianyang City, Xianyang, Shaanxi 712000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Paediatrics, The First People's Hospital of Xianyang City, Xianyang, Shaanxi 712000</wicri:regionArea></affiliation></author></analytic><series><title level="j">Experimental and Therapeutic Medicine</title><idno type="ISSN">1792-0981</idno><idno type="eISSN">1792-1015</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The role of cold inducible RNA-binding protein (CIRP) in mediating ischemic brain injury in neonatal rats under chronic hypobaric hypoxia was investigated. The neonatal rat model of chronic hypobaric hypoxia and the cell culture model of SH-SY5Y cells exposed to hypoxia (1% O<sub>2</sub>) were constructed. The expression of CIRP and hypoxia-inducible factor-1α (HIF-1α) was detected after hypoxic exposure, and the apoptosis-related proteins were analyzed via terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and western blot analysis to detect neuronal apoptosis. Moreover, the effects of CIRP overexpression on HIF-1α and neuronal apoptosis were identified. Chronic hypobaric hypoxia can lead to HIF-1α expression and neuronal apoptosis in the body. CIRP was induced at early exposure (3 d/7 d). However, the CIRP level in the hypoxic group was obviously lower than that in the control group with the prolongation of exposure time (21 d). In addition, the knockdown of HIF-1α significantly reduced the neuronal apoptosis under hypoxic conditions, indicating that HIF-1α may promote apoptosis during exposure. The overexpression of CIRP significantly inhibited the upregulation of HIF-1α during hypoxia and the HIF-1α-mediated neuronal apoptosis. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Exp Ther Med</journal-id><journal-id journal-id-type="iso-abbrev">Exp Ther Med</journal-id><journal-id journal-id-type="publisher-id">ETM</journal-id><journal-title-group><journal-title>Experimental and Therapeutic Medicine</journal-title></journal-title-group><issn pub-type="ppub">1792-0981</issn><issn pub-type="epub">1792-1015</issn><publisher><publisher-name>D.A. Spandidos</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31410103</article-id><article-id pub-id-type="pmc">6676150</article-id><article-id pub-id-type="doi">10.3892/etm.2019.7767</article-id><article-id pub-id-type="publisher-id">ETM-0-0-7767</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Lifang</given-names></name><xref ref-type="aff" rid="af1-etm-0-0-7767">1</xref></contrib><contrib contrib-type="author"><name><surname>Tian</surname><given-names>Qiaohuan</given-names></name><xref ref-type="aff" rid="af1-etm-0-0-7767">1</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Weihua</given-names></name><xref ref-type="aff" rid="af2-etm-0-0-7767">2</xref><xref rid="c1-etm-0-0-7767" ref-type="corresp"></xref></contrib></contrib-group><aff id="af1-etm-0-0-7767"><label>1</label>Department of Paediatrics, Liaocheng Third People's Hospital, Liaocheng, Shandong 252000, P.R. China</aff><aff id="af2-etm-0-0-7767"><label>2</label>Department of Paediatrics, The First People's Hospital of Xianyang City, Xianyang, Shaanxi 712000, P.R. China</aff><author-notes><corresp id="c1-etm-0-0-7767"><italic>Correspondence to</italic>: Dr Weihua Wang, Department of Paediatrics, The First People's Hospital of Xianyang City, 10 Biyuan Road, Xianyang, Shaanxi 712000, P.R. China, E-mail: <email>zi14466@163.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>9</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>11</day><month>7</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>11</day><month>7</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>18</volume><issue>3</issue><fpage>1515</fpage><lpage>1520</lpage><history><date date-type="received"><day>15</day><month>6</month><year>2018</year></date><date date-type="accepted"><day>17</day><month>4</month><year>2019</year></date></history><permissions><copyright-statement>Copyright: © Chen et al.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-NonCommercial-NoDerivs License</ext-link>, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</license-p></license></permissions><abstract><p>The role of cold inducible RNA-binding protein (CIRP) in mediating ischemic brain injury in neonatal rats under chronic hypobaric hypoxia was investigated. The neonatal rat model of chronic hypobaric hypoxia and the cell culture model of SH-SY5Y cells exposed to hypoxia (1% O<sub>2</sub>) were constructed. The expression of CIRP and hypoxia-inducible factor-1α (HIF-1α) was detected after hypoxic exposure, and the apoptosis-related proteins were analyzed via terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and western blot analysis to detect neuronal apoptosis. Moreover, the effects of CIRP overexpression on HIF-1α and neuronal apoptosis were identified. Chronic hypobaric hypoxia can lead to HIF-1α expression and neuronal apoptosis in the body. CIRP was induced at early exposure (3 d/7 d). However, the CIRP level in the hypoxic group was obviously lower than that in the control group with the prolongation of exposure time (21 d). In addition, the knockdown of HIF-1α significantly reduced the neuronal apoptosis under hypoxic conditions, indicating that HIF-1α may promote apoptosis during exposure. The overexpression of CIRP significantly inhibited the upregulation of HIF-1α during hypoxia and the HIF-1α-mediated neuronal apoptosis. Results of the current study showed that, CIRP is involved in the ischemic brain injury induced by chronic hypoxia through downregulation of HIF-1α expression.</p></abstract><kwd-group><kwd>CIRP</kwd><kwd>chronic hypobaric hypoxia</kwd><kwd>apoptosis</kwd><kwd>brain injury</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-etm-0-0-7767" orientation="portrait" position="float"><label>Figure 1.</label><caption><p>Exposure to chronic hypobaric hypoxia leads to increased apoptosis of hippocampal neurons in rats and significant changes in CIRP expression. (A and B) The relative ratios of cleaved caspase-3/caspase-3 and Bax/Bcl-2 increased significantly in the exposure group at day 7 and 21, compared with the control group. (C) Western blot analysis of CIRP in the hippocampus of rats in control group and hypobaric hypoxia group at day 3, 7 and 21. The content of CIRP in hypoxia group at day 3 and 7 is significantly increased, and it is significantly lower in hypobaric hypoxia group at day 21 than that in the control group. *P<0.05, **P<0.01. CIRP, cold inducible RNA-binding protein.</p></caption><graphic xlink:href="etm-18-03-1515-g00"></graphic></fig><fig id="f2-etm-0-0-7767" orientation="portrait" position="float"><label>Figure 2.</label><caption><p>Exposure to chronic hypobaric hypoxia leads to the increased apoptosis of hippocampal neurons in rats and significant changes in CIRP expression. (A) Flow cytometry showed 48 h SH-SY5Y cell apoptosis in control and hypobaric hypoxia group. (B and C) The relative ratios of cleaved caspase-3/caspase-3 and Bax/Bcl-2 in the hippocampus of rats in control group and hypobaric hypoxia group. (D) Western blot analysis of CIRP in the SH-SY5Y cells cultured under normoxia or hypoxia for 48 h. Compared with the normoxic group, the expression of CIRP in the hypoxic group decreased significantly. *P<0.05, **P<0.01.</p></caption><graphic xlink:href="etm-18-03-1515-g01"></graphic></fig><fig id="f3-etm-0-0-7767" orientation="portrait" position="float"><label>Figure 3.</label><caption><p>The effect of CIRP overexpression on HIF-1α expression and neuronal apoptosis. (A) The apoptosis of neurons in hypoxic group decreased significantly after pEGFP-N2-CIRP infection (P<0.01). (B) The expression of HIF-1α in hypoxic group decreased significantly after pEGFP-N2-CIRP infection (P<0.01). (C) The expression of CIRP in hypoxic group increased significantly after pEGFP-N2-CIRP infection (P<0.01). **P<0.01.</p></caption><graphic xlink:href="etm-18-03-1515-g02"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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