The impact of hemoglobin oxidation in NLRP3 inflammasome activation upon intravascular hemolysis
dc.contributor.advisor | Viktoria, Jeney | |
dc.contributor.author | Nyakundi, Bogonko Benard | |
dc.contributor.department | Molekuláris sejt- és immunbiológia doktori iskola | hu |
dc.contributor.submitterdep | DE--Általános Orvostudományi Kar -- Research Centre for Molecular Medicine | |
dc.date.accessioned | 2020-09-04T08:21:39Z | |
dc.date.available | 2020-09-04T08:21:39Z | |
dc.date.created | 2020 | hu_HU |
dc.date.defended | 2020-09-10 | |
dc.description.abstract | In 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.extent | 64 | hu_HU |
dc.identifier.uri | http://hdl.handle.net/2437/293794 | |
dc.language.iso | en | hu_HU |
dc.subject | hemolysis | hu_HU |
dc.subject | hemoglobin | |
dc.subject | inflammasome activation | |
dc.subject.discipline | Elméleti orvostudományok | hu |
dc.subject.sciencefield | Orvostudományok | hu |
dc.title | The impact of hemoglobin oxidation in NLRP3 inflammasome activation upon intravascular hemolysis | hu_HU |
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