Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats
Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PP...
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| Veröffentlicht in: | Cellular and molecular neurobiology 2023-04, Vol.43 (3), p.1355-1367 |
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| creator | Zhang, Ling-Yan Liu, Xi-Yun Su, A.-chou Hu, Yu-Yan Zhang, Jing-Ge Xian, Xiao-Hui Li, Wen-Bin Zhang, Min |
| description | Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP. First we investigated the expression of Klotho during the brain ischemic tolerance induced by CIP. Lethal ischemia significantly decreased Klotho expression from 6 h to 7 days, while CIP significantly increased Klotho expression from 12 h to 7 days in the hippocampal CA1 region. Inhibition of Klotho expression by its shRNA blocked the neuroprotection induced by CIP. These results indicate that Klotho participates in brain ischemic tolerance by CIP. Furthermore, we tested the role of PPARγ in regulating Klotho expression after CIP. CIP caused PPARγ protein translocation to the nucleus in neurons in the CA1 region of the hippocampus. Pretreatment with GW9962, a PPARγ inhibitor, significantly attenuated the upregulation of Klotho protein and blocked the brain ischemic tolerance induced by CIP. Taken together, it can be concluded that Klotho upregulation via PPARγ contributes to the induction of brain ischemic tolerance by CIP. |
| doi_str_mv | 10.1007/s10571-022-01255-y |
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However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP. First we investigated the expression of Klotho during the brain ischemic tolerance induced by CIP. Lethal ischemia significantly decreased Klotho expression from 6 h to 7 days, while CIP significantly increased Klotho expression from 12 h to 7 days in the hippocampal CA1 region. Inhibition of Klotho expression by its shRNA blocked the neuroprotection induced by CIP. These results indicate that Klotho participates in brain ischemic tolerance by CIP. Furthermore, we tested the role of PPARγ in regulating Klotho expression after CIP. CIP caused PPARγ protein translocation to the nucleus in neurons in the CA1 region of the hippocampus. Pretreatment with GW9962, a PPARγ inhibitor, significantly attenuated the upregulation of Klotho protein and blocked the brain ischemic tolerance induced by CIP. Taken together, it can be concluded that Klotho upregulation via PPARγ contributes to the induction of brain ischemic tolerance by CIP.</description><identifier>ISSN: 0272-4340</identifier><identifier>EISSN: 1573-6830</identifier><identifier>DOI: 10.1007/s10571-022-01255-y</identifier><identifier>PMID: 35900650</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Brain Ischemia - metabolism ; CA1 Region, Hippocampal ; Cell Biology ; Hippocampus ; Ischemia ; Ischemic Preconditioning ; Klotho protein ; Neurobiology ; Neuroprotection ; Neurosciences ; Original Research ; Peroxisome proliferator-activated receptors ; PPAR gamma - metabolism ; Protein transport ; Rats ; Rats, Wistar ; Up-Regulation</subject><ispartof>Cellular and molecular neurobiology, 2023-04, Vol.43 (3), p.1355-1367</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-94c974e2d199688d611ae06c175654085f8eb46f051d442bd347837806a245503</citedby><cites>FETCH-LOGICAL-c375t-94c974e2d199688d611ae06c175654085f8eb46f051d442bd347837806a245503</cites><orcidid>0000-0002-2176-8532</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10571-022-01255-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10571-022-01255-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35900650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Ling-Yan</creatorcontrib><creatorcontrib>Liu, Xi-Yun</creatorcontrib><creatorcontrib>Su, A.-chou</creatorcontrib><creatorcontrib>Hu, Yu-Yan</creatorcontrib><creatorcontrib>Zhang, Jing-Ge</creatorcontrib><creatorcontrib>Xian, Xiao-Hui</creatorcontrib><creatorcontrib>Li, Wen-Bin</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><title>Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats</title><title>Cellular and molecular neurobiology</title><addtitle>Cell Mol Neurobiol</addtitle><addtitle>Cell Mol Neurobiol</addtitle><description>Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP. First we investigated the expression of Klotho during the brain ischemic tolerance induced by CIP. Lethal ischemia significantly decreased Klotho expression from 6 h to 7 days, while CIP significantly increased Klotho expression from 12 h to 7 days in the hippocampal CA1 region. Inhibition of Klotho expression by its shRNA blocked the neuroprotection induced by CIP. These results indicate that Klotho participates in brain ischemic tolerance by CIP. Furthermore, we tested the role of PPARγ in regulating Klotho expression after CIP. CIP caused PPARγ protein translocation to the nucleus in neurons in the CA1 region of the hippocampus. Pretreatment with GW9962, a PPARγ inhibitor, significantly attenuated the upregulation of Klotho protein and blocked the brain ischemic tolerance induced by CIP. Taken together, it can be concluded that Klotho upregulation via PPARγ contributes to the induction of brain ischemic tolerance by CIP.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain Ischemia - metabolism</subject><subject>CA1 Region, Hippocampal</subject><subject>Cell Biology</subject><subject>Hippocampus</subject><subject>Ischemia</subject><subject>Ischemic Preconditioning</subject><subject>Klotho protein</subject><subject>Neurobiology</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Original Research</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>PPAR gamma - metabolism</subject><subject>Protein transport</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Up-Regulation</subject><issn>0272-4340</issn><issn>1573-6830</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAURi0EokPhBVggS2zYpFz_J8syAjqiEqOqXVuOczOTKmMPdoI0e96I9-CZcDuFSixY2dI93-crH0JeMzhjAOZ9ZqAMq4DzChhXqjo8IQumjKh0LeApWQA3vJJCwgl5kfMtADQA6jk5EapctIIF-fFljNM20pt9ws08ummIgX4fHF2vz69-_aTLGKY0tPOEmU6RTlukq9DN_p6LPf2Q3BDoKvst7gZPr-OIyQWPtD3QJSZskxsfx-uEPoZuuEsPYUNL9MpN-SV51rsx46uH85TcfPp4vbyoLr9-Xi3PLysvjJqqRvrGSOQdaxpd151mzCFoz4zSSkKt-hpbqXtQrJOSt52QphamBu24VArEKXl37N2n-G3GPNndkD2OowsY52y5bnT5I9WIgr79B72NcwplO8tNrbQuvapQ_Ej5FHNO2Nt9GnYuHSwDe-fIHh3Z4sjeO7KHEnrzUD23O-z-Rv5IKYA4ArmMwgbT49v_qf0NjyqcoA</recordid><startdate>20230401</startdate><enddate>20230401</enddate><creator>Zhang, Ling-Yan</creator><creator>Liu, Xi-Yun</creator><creator>Su, A.-chou</creator><creator>Hu, Yu-Yan</creator><creator>Zhang, Jing-Ge</creator><creator>Xian, Xiao-Hui</creator><creator>Li, Wen-Bin</creator><creator>Zhang, Min</creator><general>Springer US</general><general>Springer Nature B.V</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><orcidid>https://orcid.org/0000-0002-2176-8532</orcidid></search><sort><creationdate>20230401</creationdate><title>Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats</title><author>Zhang, Ling-Yan ; Liu, Xi-Yun ; Su, A.-chou ; Hu, Yu-Yan ; Zhang, Jing-Ge ; Xian, Xiao-Hui ; Li, Wen-Bin ; Zhang, Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-94c974e2d199688d611ae06c175654085f8eb46f051d442bd347837806a245503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain Ischemia - metabolism</topic><topic>CA1 Region, Hippocampal</topic><topic>Cell Biology</topic><topic>Hippocampus</topic><topic>Ischemia</topic><topic>Ischemic Preconditioning</topic><topic>Klotho protein</topic><topic>Neurobiology</topic><topic>Neuroprotection</topic><topic>Neurosciences</topic><topic>Original Research</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>PPAR gamma - metabolism</topic><topic>Protein transport</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Ling-Yan</creatorcontrib><creatorcontrib>Liu, Xi-Yun</creatorcontrib><creatorcontrib>Su, A.-chou</creatorcontrib><creatorcontrib>Hu, Yu-Yan</creatorcontrib><creatorcontrib>Zhang, Jing-Ge</creatorcontrib><creatorcontrib>Xian, Xiao-Hui</creatorcontrib><creatorcontrib>Li, Wen-Bin</creatorcontrib><creatorcontrib>Zhang, Min</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>Cellular and molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Ling-Yan</au><au>Liu, Xi-Yun</au><au>Su, A.-chou</au><au>Hu, Yu-Yan</au><au>Zhang, Jing-Ge</au><au>Xian, Xiao-Hui</au><au>Li, Wen-Bin</au><au>Zhang, Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats</atitle><jtitle>Cellular and molecular neurobiology</jtitle><stitle>Cell Mol Neurobiol</stitle><addtitle>Cell Mol Neurobiol</addtitle><date>2023-04-01</date><risdate>2023</risdate><volume>43</volume><issue>3</issue><spage>1355</spage><epage>1367</epage><pages>1355-1367</pages><issn>0272-4340</issn><eissn>1573-6830</eissn><abstract>Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP. First we investigated the expression of Klotho during the brain ischemic tolerance induced by CIP. Lethal ischemia significantly decreased Klotho expression from 6 h to 7 days, while CIP significantly increased Klotho expression from 12 h to 7 days in the hippocampal CA1 region. Inhibition of Klotho expression by its shRNA blocked the neuroprotection induced by CIP. These results indicate that Klotho participates in brain ischemic tolerance by CIP. Furthermore, we tested the role of PPARγ in regulating Klotho expression after CIP. CIP caused PPARγ protein translocation to the nucleus in neurons in the CA1 region of the hippocampus. Pretreatment with GW9962, a PPARγ inhibitor, significantly attenuated the upregulation of Klotho protein and blocked the brain ischemic tolerance induced by CIP. Taken together, it can be concluded that Klotho upregulation via PPARγ contributes to the induction of brain ischemic tolerance by CIP.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>35900650</pmid><doi>10.1007/s10571-022-01255-y</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-2176-8532</orcidid></addata></record> |
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| subjects | Animals Biomedical and Life Sciences Biomedicine Brain Ischemia - metabolism CA1 Region, Hippocampal Cell Biology Hippocampus Ischemia Ischemic Preconditioning Klotho protein Neurobiology Neuroprotection Neurosciences Original Research Peroxisome proliferator-activated receptors PPAR gamma - metabolism Protein transport Rats Rats, Wistar Up-Regulation |
| title | Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats |
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