Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia.
DC Field | Value | Language |
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dc.contributor.author | Joo, Eun Jung | - |
dc.contributor.author | Gab, Seok Kim | - |
dc.contributor.author | Purnima Narasim | - |
dc.contributor.author | Song, Yun Seon | - |
dc.contributor.author | Chan PH | - |
dc.date.available | 2021-02-22T14:17:36Z | - |
dc.date.issued | 2009-05 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.issn | 1529-2401 | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13783 | - |
dc.description.abstract | Cerebral ischemia and reperfusion increase superoxide anions (O 2.-) in brain mitochondria. Manganese superoxide dismutase (Mn-SOD; SOD2), a primary mitochondrial antioxidant enzyme, scavenges superoxide radicals and its overexpression provides neuroprotection. However, the regulatory mechanism of Mn-SOD expression during cerebral ischemia and reperfusion is still unclear. In this study, we identified the signal transducer and activator of transcription 3 (STAT3) as a transcription factor of the mouse Mn-SOD gene, and elucidated the mechanism of O2.- overproduction after transient focal cerebral ischemia (tFCI). We found that Mn-SOD expression is significantly reduced by reperfusion in the cerebral ischemic brain. We also found that activated STAT3 is usually recruited into the mouse Mn-SOD promoter and upregulates transcription of the mouse Mn-SOD gene in the normal brain. However, at early postreperfusion periods after tFCI, STAT3 was rapidly downregulated, and its recruitment into the Mn-SOD promoter was completely blocked. In addition, transcriptional activity of the mouse Mn-SOD gene was significantly reduced by STAT3 inhibition in primary cortical neurons. Moreover, we found that STAT3 deactivated by reperfusion induces accumulation of O2.- in mitochondria. The loss of STAT3 activity induced neuronal cell death by reducing Mn-SOD expression. Using SOD2-/+ heterozygous knock-out mice, we found that Mn-SOD is a direct target of STAT3 in reperfusion-induced neuronal cell death. Our study demonstrates that STAT3 is a novel transcription factor of the mouse Mn-SOD gene and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the mouse brain. Copyright © 2009 Society for Neuroscience. | - |
dc.format.extent | 12 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | SOC NEUROSCIENCE | - |
dc.title | Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia. | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1523/JNEUROSCI.1110-09.2009 | - |
dc.identifier.scopusid | 2-s2.0-66149171367 | - |
dc.identifier.wosid | 000266438800026 | - |
dc.identifier.bibliographicCitation | JOURNAL OF NEUROSCIENCE, v.29, no.21, pp 7003 - 7014 | - |
dc.citation.title | JOURNAL OF NEUROSCIENCE | - |
dc.citation.volume | 29 | - |
dc.citation.number | 21 | - |
dc.citation.startPage | 7003 | - |
dc.citation.endPage | 7014 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.identifier.url | https://www.jneurosci.org/content/29/21/7003/tab-figures-data | - |
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