Activated Microglia Are Less Vulnerable to Hemin Toxicity due to Nitric Oxide-Dependent Inhibition of JNK and p38 MAPK Activation
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cai, Ying | - |
dc.contributor.author | Cho, Geum-Sil | - |
dc.contributor.author | Ju, Chung | - |
dc.contributor.author | Wang, Si-Ling | - |
dc.contributor.author | Ryu, Jong Hoon | - |
dc.contributor.author | Shin, Chan Young | - |
dc.contributor.author | Kim, Hee-Sun | - |
dc.contributor.author | Nam, Kung-Woo | - |
dc.contributor.author | Jalin, Angela M. A. Anthony | - |
dc.contributor.author | Sun, Woong | - |
dc.contributor.author | Choi, In-Young | - |
dc.contributor.author | Kim, Won-Ki | - |
dc.date.accessioned | 2022-01-03T07:41:41Z | - |
dc.date.available | 2022-01-03T07:41:41Z | - |
dc.date.created | 2021-08-30 | - |
dc.date.issued | 2011-08-01 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/134221 | - |
dc.description.abstract | In intracerebral hemorrhage, microglia become rapidly activated and remove the deposited blood and cellular debris. To survive in a harmful hemorrhagic or posthemorrhagic condition, activated microglia must be equipped with appropriate self-defensive mechanism(s) to resist the toxicity of hemin, a component released from damaged RBCs. In the current study, we found that activation of microglia by pretreatment with LPS markedly reduced their vulnerability to hemin toxicity in vitro. Similarly, intracorpus callosum microinjection of LPS prior to hemin treatment reduced the brain tissue damage caused by hemin and increased microglial density in the penumbra in rats. LPS induced the expressions of inducible NO synthase (iNOS) and heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation in microglia. The preventive effect by LPS was significantly diminished by an iNOS inhibitor, L-N(6)-(1-iminoethyl)lysine, whereas it was mimicked by a NO donor, diethylamine-NONOate, both suggesting the crucial role of NO in the modulation of hemin-induced toxicity in activated microglia. We further found that NO reduced hemin toxicity via inhibition of hemin-induced activation of JNK and p38 MAPK pathways in microglia. Whereas HO-1 expression in LPS-stimulated microglia was markedly blocked by L-N(6)-(1-iminoethyl)lysine, the HO-1 inhibitor, tin protoporphyrin, increased iNOS expression and decreased the susceptibility of LPS-activated microglia to hemin toxicity. The data indicate that the mutual interaction between NO and HO-1 plays a critical role in modulating the adaptive response of activated microglia to hemin toxicity. Better understanding of the survival mechanism of activated microglia may provide a therapeutic strategy to attenuate the devastating intracerebral hemorrhagic injury. The Journal of Immunology, 2011, 187: 1314-1321. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.subject | INTRACEREBRAL HEMORRHAGE TREATMENT | - |
dc.subject | BRAIN-INJURY | - |
dc.subject | OXYGENASE-1 INDUCTION | - |
dc.subject | TIN-MESOPORPHYRIN | - |
dc.subject | CORTICAL-NEURONS | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | INDUCED DEATH | - |
dc.subject | ASTROCYTES | - |
dc.subject | CELLS | - |
dc.subject | LIPOPOLYSACCHARIDE | - |
dc.title | Activated Microglia Are Less Vulnerable to Hemin Toxicity due to Nitric Oxide-Dependent Inhibition of JNK and p38 MAPK Activation | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Sun, Woong | - |
dc.contributor.affiliatedAuthor | Choi, In-Young | - |
dc.contributor.affiliatedAuthor | Kim, Won-Ki | - |
dc.identifier.doi | 10.4049/jimmunol.1002925 | - |
dc.identifier.scopusid | 2-s2.0-80051610850 | - |
dc.identifier.wosid | 000292874200032 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.187, no.3, pp.1314 - 1321 | - |
dc.relation.isPartOf | JOURNAL OF IMMUNOLOGY | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 187 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1314 | - |
dc.citation.endPage | 1321 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | INTRACEREBRAL HEMORRHAGE TREATMENT | - |
dc.subject.keywordPlus | BRAIN-INJURY | - |
dc.subject.keywordPlus | OXYGENASE-1 INDUCTION | - |
dc.subject.keywordPlus | TIN-MESOPORPHYRIN | - |
dc.subject.keywordPlus | CORTICAL-NEURONS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | INDUCED DEATH | - |
dc.subject.keywordPlus | ASTROCYTES | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | LIPOPOLYSACCHARIDE | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.