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001-es BibID:BIBFORM072211
035-os BibID:(cikkazonosító)4310816 (PMID)29743981 (PMCID)PMC5883980
Első szerző:Erdei Judit Zsuzsa (vegyész)
Cím:Induction Of NLRP3 Inflammasome Activation By Heme In Human Endothelial Cells / Judit Erdei, Andrea Tóth, Enikő Balogh, Benard Bogonko Nyakundi, Emese Bányai, Bernhard Ryffel, György Paragh, Mario D. Cordero, Viktória Jeney
Dátum:2018
ISSN:1942-0994 1942-0900
Megjegyzések:Hemolytic or hemorrhagic episodes are often associated with inflammation even when infectious agents are absent suggesting that red blood cells (RBCs) release damage-associated molecular patterns (DAMPs). DAMPs activate immune and nonimmune cells through pattern recognition receptors. Heme, released from RBCs, is a DAMP and induces IL-1β production through the activation of the nucleotide-binding domain and leucine-rich repeat-containing family and pyrin domain containing 3 (NLRP3) in macrophages; however, other cellular targets of heme-mediated inflammasome activation were not investigated. Because of their location, endothelial cells can be largely exposed to RBC-derived DAMPs; therefore, we investigated whether heme and other hemoglobin- (Hb-) derived species induce NLRP3 inflammasome activation in these cells. We found that heme upregulated NLRP3 expression and induced active IL-1β production in human umbilical vein endothelial cells (HUVECs). LPS priming largely amplified the heme-mediated production of IL-1β. Heme administration into C57BL/6 mice induced caspase-1 activation and cleavage of IL-1β which was not observed in NLRP3?/? mice. Unfettered production of reactive oxygen species played a critical role in heme-mediated NLRP3 activation. Activation of NLRP3 by heme required structural integrity of the heme molecule, as neither protoporphyrin IX nor iron-induced IL-1β production. Neither naive nor oxidized forms of Hb were able to induce IL-1β production in HUVECs. Our results identified endothelial cells as a target of heme-mediated NLRP3 activation that can contribute to the inflammation triggered by sterile hemolysis. Thus, understanding the characteristics and cellular counterparts of RBC-derived DAMPs might allow us to identify new therapeutic targets for hemolytic diseases.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Heme
endothelial cells
hemolysis
hemoglobin
DAMP
NLRP3 inflammasome activation
IL-1?
ROS
Megjelenés:Oxidative Medicine and Cellular Longevity. - 2018 (2018), p. 1-14. -
További szerzők:Tóth Andrea (1992-) (molekuláris biológus) Balogh Enikő (1987-) (molekuláris biológus) Nyakundi, Benard Bogonko (1983-) (biokémikus) Bányai Emese (1984-) (orvos) Ryffel, Bernhard Paragh György (1953-) (belgyógyász) Cordero, Mario D. Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:NKFIH K116024
Egyéb
GINOP-2.3.2-15-2016-00005
GINOP
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2.

001-es BibID:BIBFORM085378
035-os BibID:(cikkazonosító)8929020
Első szerző:Nyakundi, Benard Bogonko (biokémikus)
Cím:Formation and Detection of Highly Oxidized Hemoglobin Forms in Biological Fluids during Hemolytic Conditions / Nyakundi Benard Bogonko, Erdei Judit, Tóth Andrea, Balogh Enikő, Nagy Andrea, Nagy Béla Jr., Novák László, Bognár László, Paragh György, Kappelmayer János, Jeney Viktória
Dátum:2020
ISSN:1942-0900 1942-0994
Megjegyzések:Hemolytic diseases are characterized by an accelerated breakdown of red blood cells (RBCs) and the release of hemoglobin (Hb). Following, RBC lysis Hb oxidation occurs with the formation of different redox states of Hb (metHb and ferrylHb) and the release of heme. ferrylHb is unstable and decomposes to metHb with the concomitant formation of globin radicals and eventually covalently crosslinked Hb multimers. The goal of the present study was to determine the concentrations of the different redox states of Hb in biological samples during hemolytic conditions. We used plasma and urine samples of mice with intravascular hemolysis and human cerebrospinal fluid (CSF) samples following intraventricular hemorrhage. Because ferrylHb is highly unstable, we also addressed the fate of this species. metHb and free heme time-dependently accumulate in plasma and CSF samples following intravascular hemolysis and intraventricular hemorrhage, respectively. ferrylHb is hardly detectable in the biological samples during hemolytic conditions. Under in vitro conditions, ferrylHb decomposes quickly to metHb, which process is associated with the formation of covalently crosslinked Hb multimers. We detected these covalently crosslinked Hb multimers in plasma, urine, and CSF samples during hemolytic conditions. Because globin modification is specific for these Hb forms, we propose to call this heterogeneous form of Hb produced during ferrylHb decomposition as globin-modified oxidized Hb (gmoxHb). Understanding the formation and the contribution of gmoxHb species to the pathogenesis of hemolytic conditions could have therapeutic implications in the treatment of hemolytic diseases.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Oxidative Medicine and Cellular Longevity. - 2020 (2020), p. 1-13. -
További szerzők:Erdei Judit Zsuzsa (1992-) (vegyész) Tóth Andrea (1992-) (molekuláris biológus) Balogh Enikő (1987-) (molekuláris biológus) Nagy Andrea (1958-) (csecsemő és gyermekgyógyász, neonatológus) Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos) Novák László (1964-) (idegsebész) Bognár László (1958-) (idegsebész, gyermekidegsebész) Paragh György (1953-) (belgyógyász) Kappelmayer János (1960-) (laboratóriumi szakorvos) Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:GINOP-2.3.2-15-2016-00005
GINOP
Internet cím:Szerző által megadott URL
DOI
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