{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:45:30Z","timestamp":1788371130534,"version":"build-2803163510"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,14]],"date-time":"2022-08-14T00:00:00Z","timestamp":1660435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2018YFA0108003"],"award-info":[{"award-number":["2018YFA0108003"]}]},{"name":"the National Key Research and Development Program of China","award":["XDA16010309"],"award-info":[{"award-number":["XDA16010309"]}]},{"name":"the National Key Research and Development Program of China","award":["81901094"],"award-info":[{"award-number":["81901094"]}]},{"name":"the \u201cStrategic Priority Research Program\u201d of the Chinese Academy of Sciences","award":["2018YFA0108003"],"award-info":[{"award-number":["2018YFA0108003"]}]},{"name":"the \u201cStrategic Priority Research Program\u201d of the Chinese Academy of Sciences","award":["XDA16010309"],"award-info":[{"award-number":["XDA16010309"]}]},{"name":"the \u201cStrategic Priority Research Program\u201d of the Chinese Academy of Sciences","award":["81901094"],"award-info":[{"award-number":["81901094"]}]},{"name":"the National Science Foundation for Young Scientists of China","award":["2018YFA0108003"],"award-info":[{"award-number":["2018YFA0108003"]}]},{"name":"the National Science Foundation for Young Scientists of China","award":["XDA16010309"],"award-info":[{"award-number":["XDA16010309"]}]},{"name":"the National Science Foundation for Young Scientists of China","award":["81901094"],"award-info":[{"award-number":["81901094"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Structural and functional alterations of vasculature caused by age-related factors is critically involved in the pathogenesis of ischemic stroke. The longevity genes sirtuins (SIRTs) are extensively investigated in aging-associated pathologies, but their distinct roles in ischemic stroke still remain to be clarified. To address this question, we applied oxygen and glucose deprived\/reperfusion (OGD\/R) to induce ischemic injury in human endothelial cells (ECs), which are the main component of vasculature in the brain. The results showed that OGD\/R led to various damages to ECs, including compromised cell viability, increased LDH release, overproduced ROS, enhanced apoptosis and caspase activity. Meanwhile, the expression of mitochondrial SIRT3 was robustly decreased in ECs after OGD\/R treatment. Consistently, rescue of SIRT3 by ectopic expression, but not nuclear SIRT1, in ECs reversed the OGD\/R-induced cell damage. Interestingly, some front-line drugs for ischemic stroke, including clopidogrel, aspirin and dl-3-n-butylphthalide (NBP), also rescued SIRT3 and reduced OGD\/R-induced endothelial injury, suggesting that the recovery of SIRT3 expression was critical for the protection of these drugs. Moreover, our results demonstrated that 10-hydroxy-NBP (OHNBP), a major metabolite of NBP, showed better blood-brain barrier crossing capability than NBP, but still retained the effects on SIRT3 by NBP. Together, our results suggested that SIRT3 may serve as a potential novel target for treatment of ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms23169118","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T01:47:21Z","timestamp":1660528041000},"page":"9118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Rescue of Mitochondrial SIRT3 Ameliorates Ischemia-like Injury in Human Endothelial Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Xi","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Pei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Biomedicine, The Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200070, China"},{"name":"Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichao","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,14]]},"reference":[{"key":"ref_1","first-page":"268","article-title":"Update on treatment of acute ischemic stroke","volume":"26","author":"Rabinstein","year":"2020","journal-title":"Continuum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.2174\/1871527317666180612125843","article-title":"Dl-3-n-butylphthalide (nbp): A promising therapeutic agent for ischemic stroke","volume":"17","author":"Wang","year":"2018","journal-title":"CNS Neurol. 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