Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons
Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocam...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2017-05, Vol.486 (4), p.1005-1013 |
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| creator | Zhou, Tianen Liang, Yanran Jiang, Longyuan Yu, Tao Zeng, Chaotao Tao, Enxiang |
| description | Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocampal neurons. However, the mechanisms behind the activation of caspase-3 remain unclear. The aims of this study were to determine whether the protective effects of mild hypothermia were exerted through the Wnt/β-catenin signaling pathway. We found that, under OGD/R conditions, the pathway was down regulated, but mild hypothermia induced the reactivation of the Wnt/β-catenin signaling pathway, which had been suppressed by OGD/R injury. Mild hypothermia also caused the down regulation of the expression of apoptosis promoting proteins (Bax cleaved caspase-3), up-regulated the expression of apoptosis inhibiting proteins (Bcl-2), and ameliorated OGD/R injury-induced apoptosis. The protective effects of mild hypothermia were blocked by DKK1 (an antagonist of the canonical Wnt signaling pathway). Taken together, these results indicate that the Wnt/β-catenin signaling pathway mediates the protective effects of mild hypothermia against OGD/R-induced apoptosis. Our study provides evidence that mild hypothermia reactivates the Wnt/β-catenin signaling pathway, which is suppressed by OGD/R injury, in hippocampal neurons and protects neurons from OGD/R-induced apoptosis via the reactivation of the Wnt/β-catenin signaling pathway, ultimately suggesting that mild hypothermia could have therapeutic effects on OGD/R-induced apoptosis.
•The Wnt/β-catenin signaling pathway mediates the expression levels of apoptosis-related proteins.•OGD/R suppresses the Wnt/β‑catenin signaling pathway and induces apoptosis in hippocampal neurons.•Mild hypothermia induces the reactivation of the Wnt/β-catenin signaling pathway.•Mild hypothermia protects neurons from OGD/R-induced apoptosis via reactivation of the Wnt/β-catenin signaling pathway. |
| doi_str_mv | 10.1016/j.bbrc.2017.03.153 |
| format | Article |
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•The Wnt/β-catenin signaling pathway mediates the expression levels of apoptosis-related proteins.•OGD/R suppresses the Wnt/β‑catenin signaling pathway and induces apoptosis in hippocampal neurons.•Mild hypothermia induces the reactivation of the Wnt/β-catenin signaling pathway.•Mild hypothermia protects neurons from OGD/R-induced apoptosis via reactivation of the Wnt/β-catenin signaling pathway.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2017.03.153</identifier><identifier>PMID: 28365156</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; beta Catenin - metabolism ; Brain Ischemia - metabolism ; Brain Ischemia - prevention & control ; Cells, Cultured ; Glucose - metabolism ; Hippocampus - metabolism ; Hippocampus - pathology ; Hypothermia, Induced - methods ; Mild hypothermia ; Neurons - metabolism ; Neurons - pathology ; OGD/R ; Oxygen - metabolism ; Rats ; Reperfusion Injury - metabolism ; Reperfusion Injury - pathology ; Reperfusion Injury - prevention & control ; Treatment Outcome ; Wnt Signaling Pathway ; Wnt/β-catenin</subject><ispartof>Biochemical and biophysical research communications, 2017-05, Vol.486 (4), p.1005-1013</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-2baea1275e28c788bc6d70edaefabb4ee984163156b56efbb3d797b13e55acd03</citedby><cites>FETCH-LOGICAL-c356t-2baea1275e28c788bc6d70edaefabb4ee984163156b56efbb3d797b13e55acd03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X17306307$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28365156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Tianen</creatorcontrib><creatorcontrib>Liang, Yanran</creatorcontrib><creatorcontrib>Jiang, Longyuan</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><creatorcontrib>Zeng, Chaotao</creatorcontrib><creatorcontrib>Tao, Enxiang</creatorcontrib><title>Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocampal neurons. However, the mechanisms behind the activation of caspase-3 remain unclear. The aims of this study were to determine whether the protective effects of mild hypothermia were exerted through the Wnt/β-catenin signaling pathway. We found that, under OGD/R conditions, the pathway was down regulated, but mild hypothermia induced the reactivation of the Wnt/β-catenin signaling pathway, which had been suppressed by OGD/R injury. Mild hypothermia also caused the down regulation of the expression of apoptosis promoting proteins (Bax cleaved caspase-3), up-regulated the expression of apoptosis inhibiting proteins (Bcl-2), and ameliorated OGD/R injury-induced apoptosis. The protective effects of mild hypothermia were blocked by DKK1 (an antagonist of the canonical Wnt signaling pathway). Taken together, these results indicate that the Wnt/β-catenin signaling pathway mediates the protective effects of mild hypothermia against OGD/R-induced apoptosis. Our study provides evidence that mild hypothermia reactivates the Wnt/β-catenin signaling pathway, which is suppressed by OGD/R injury, in hippocampal neurons and protects neurons from OGD/R-induced apoptosis via the reactivation of the Wnt/β-catenin signaling pathway, ultimately suggesting that mild hypothermia could have therapeutic effects on OGD/R-induced apoptosis.
•The Wnt/β-catenin signaling pathway mediates the expression levels of apoptosis-related proteins.•OGD/R suppresses the Wnt/β‑catenin signaling pathway and induces apoptosis in hippocampal neurons.•Mild hypothermia induces the reactivation of the Wnt/β-catenin signaling pathway.•Mild hypothermia protects neurons from OGD/R-induced apoptosis via reactivation of the Wnt/β-catenin signaling pathway.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>beta Catenin - metabolism</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - prevention & control</subject><subject>Cells, Cultured</subject><subject>Glucose - metabolism</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Hypothermia, Induced - methods</subject><subject>Mild hypothermia</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>OGD/R</subject><subject>Oxygen - metabolism</subject><subject>Rats</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - pathology</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Treatment Outcome</subject><subject>Wnt Signaling Pathway</subject><subject>Wnt/β-catenin</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuOFCEUhonROO3oC7gwLN1UNRR1TdyYibdkjBuN7sgBTlfTqYISqNZ-F5_CB_GZpO3RpSsC_OdL_vMR8pSzkjPebg-lUkGXFeNdyUTJG3GPbDgbWFFxVt8nG8ZYW1QD_3JFHsV4YIzzuh0ekquqF23Dm3ZDfry3k6H70-LTHsNsgS7BJ9QpUhjBupio_34a0dFxWrWPSA0uwR4hWe-2AS-ff26FdWbVaCgsfkk-2kiPmZe59LNL218_Cw0JnXU02tHBZN1IF0j7b3Ci-XFvl8VrmBeYqMM1eBcfkwc7mCI-uTuvyafXrz7evC1uP7x5d_PyttCiaVNRKUDgVddg1euu75VuTcfQAO5AqRpx6GveitxXNS3ulBKmGzrFBTYNaMPENXl-4ebuX1eMSc42apwmcOjXKHnfi75mg-hytLpEdfAxBtzJvI0ZwklyJs9W5EGercizFcmEzFby0LM7_qpmNP9G_mrIgReXAOaWR4tBRm3R5WXakF1I4-3_-L8BFh6k8g</recordid><startdate>20170513</startdate><enddate>20170513</enddate><creator>Zhou, Tianen</creator><creator>Liang, Yanran</creator><creator>Jiang, Longyuan</creator><creator>Yu, Tao</creator><creator>Zeng, Chaotao</creator><creator>Tao, Enxiang</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20170513</creationdate><title>Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons</title><author>Zhou, Tianen ; Liang, Yanran ; Jiang, Longyuan ; Yu, Tao ; Zeng, Chaotao ; Tao, Enxiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-2baea1275e28c788bc6d70edaefabb4ee984163156b56efbb3d797b13e55acd03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>beta Catenin - metabolism</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - prevention & control</topic><topic>Cells, Cultured</topic><topic>Glucose - metabolism</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Hypothermia, Induced - methods</topic><topic>Mild hypothermia</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>OGD/R</topic><topic>Oxygen - metabolism</topic><topic>Rats</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - pathology</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Treatment Outcome</topic><topic>Wnt Signaling Pathway</topic><topic>Wnt/β-catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Tianen</creatorcontrib><creatorcontrib>Liang, Yanran</creatorcontrib><creatorcontrib>Jiang, Longyuan</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><creatorcontrib>Zeng, Chaotao</creatorcontrib><creatorcontrib>Tao, Enxiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Tianen</au><au>Liang, Yanran</au><au>Jiang, Longyuan</au><au>Yu, Tao</au><au>Zeng, Chaotao</au><au>Tao, Enxiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2017-05-13</date><risdate>2017</risdate><volume>486</volume><issue>4</issue><spage>1005</spage><epage>1013</epage><pages>1005-1013</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocampal neurons. However, the mechanisms behind the activation of caspase-3 remain unclear. The aims of this study were to determine whether the protective effects of mild hypothermia were exerted through the Wnt/β-catenin signaling pathway. We found that, under OGD/R conditions, the pathway was down regulated, but mild hypothermia induced the reactivation of the Wnt/β-catenin signaling pathway, which had been suppressed by OGD/R injury. Mild hypothermia also caused the down regulation of the expression of apoptosis promoting proteins (Bax cleaved caspase-3), up-regulated the expression of apoptosis inhibiting proteins (Bcl-2), and ameliorated OGD/R injury-induced apoptosis. The protective effects of mild hypothermia were blocked by DKK1 (an antagonist of the canonical Wnt signaling pathway). Taken together, these results indicate that the Wnt/β-catenin signaling pathway mediates the protective effects of mild hypothermia against OGD/R-induced apoptosis. Our study provides evidence that mild hypothermia reactivates the Wnt/β-catenin signaling pathway, which is suppressed by OGD/R injury, in hippocampal neurons and protects neurons from OGD/R-induced apoptosis via the reactivation of the Wnt/β-catenin signaling pathway, ultimately suggesting that mild hypothermia could have therapeutic effects on OGD/R-induced apoptosis.
•The Wnt/β-catenin signaling pathway mediates the expression levels of apoptosis-related proteins.•OGD/R suppresses the Wnt/β‑catenin signaling pathway and induces apoptosis in hippocampal neurons.•Mild hypothermia induces the reactivation of the Wnt/β-catenin signaling pathway.•Mild hypothermia protects neurons from OGD/R-induced apoptosis via reactivation of the Wnt/β-catenin signaling pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28365156</pmid><doi>10.1016/j.bbrc.2017.03.153</doi><tpages>9</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2017-05, Vol.486 (4), p.1005-1013 |
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| subjects | Animals Apoptosis beta Catenin - metabolism Brain Ischemia - metabolism Brain Ischemia - prevention & control Cells, Cultured Glucose - metabolism Hippocampus - metabolism Hippocampus - pathology Hypothermia, Induced - methods Mild hypothermia Neurons - metabolism Neurons - pathology OGD/R Oxygen - metabolism Rats Reperfusion Injury - metabolism Reperfusion Injury - pathology Reperfusion Injury - prevention & control Treatment Outcome Wnt Signaling Pathway Wnt/β-catenin |
| title | Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons |
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