The impact of hemoglobin oxidation in NLRP3 inflammasome activation upon intravascular hemolysis

dc.contributor.advisorViktoria, Jeney
dc.contributor.authorNyakundi, Bogonko Benard
dc.contributor.departmentMolekuláris sejt- és immunbiológia doktori iskolahu
dc.contributor.submitterdepDE--Általános Orvostudományi Kar -- Research Centre for Molecular Medicine
dc.date.accessioned2020-09-04T08:21:39Z
dc.date.available2020-09-04T08:21:39Z
dc.date.created2020hu_HU
dc.date.defended2020-09-10
dc.description.abstractIn this work, we demonstrated that following intravascular hemolysis Hb oxidation leads to the formation of hemichrome, metHb, covalently cross-linked Hb multimers, and free heme. We showed that PHZ-induced IVH triggers IL-1 production via the NLRP3 inflammasome activation. We demonstrated that covalently cross-linked Hb forms during the decomposition of transient ferrylHb the molecules we proposed to name as gmoxHb. We Identified gmoxHb as a potent pro-inflammatory Hb form which induced the active production of IL-1 in vivo and in vitro. We confirmed that NLRP3 deficiency confers a survival advantage to mice in PHZ-induced IVH via increased tolerance and improved tissue damage control mechanisms. Identification of RBC-derived DAMPs and understanding the signaling mechanisms involved in the pathophysiology might provide new approaches for the treatment of IVH-related pathological conditions.hu_HU
dc.format.extent64hu_HU
dc.identifier.urihttp://hdl.handle.net/2437/293794
dc.language.isoenhu_HU
dc.subjecthemolysishu_HU
dc.subjecthemoglobin
dc.subjectinflammasome activation
dc.subject.disciplineElméleti orvostudományokhu
dc.subject.sciencefieldOrvostudományokhu
dc.titleThe impact of hemoglobin oxidation in NLRP3 inflammasome activation upon intravascular hemolysishu_HU
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