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001-es BibID:BIBFORM085388
035-os BibID:(WoS)000524776500001 (Scopus)85082380165 (cikkazonosító)228
Első szerző:Erdei Judit Zsuzsa (vegyész)
Cím:The Role of Hemoglobin Oxidation Products in Triggering Inflammatory Response Upon Intraventricular Hemorrhage in Premature Infants / Erdei Judit, Tóth Andrea, Nagy Andrea, Nyakundi Benard Bogonko, Fejes Zsolt, Nagy Béla Jr., Novák László, Bognár László, Balogh Enikö, Paragh György, Kappelmayer János, Bácsi Attila, Jeney Viktória
Dátum:2020
ISSN:1664-3224
Megjegyzések:Intraventricular hemorrhage (IVH) is a frequent complication of prematurity that is associated with high neonatal mortality and morbidity. IVH is accompanied by red blood cell (RBC) lysis, hemoglobin (Hb) oxidation, and sterile inflammation. Here we investigated whether extracellular Hb, metHb, ferrylHb, and heme contribute to the inflammatory response after IVH. We collected cerebrospinal fluid (CSF) (n = 20) from premature infants with grade III IVH at different time points after the onset of IVH. Levels of Hb, metHb, total heme, and free heme were the highest in CSF samples obtained between days 0 and 20 after the onset of IVH and were mostly non-detectable in CSF collected between days 41 and 60 of post-IVH. Besides Hb monomers, we detected cross-linked Hb dimers and tetramers in post-IVH CSF samples obtained in days 0-20 and 21-40, but only Hb tetramers were present in CSF samples obtained after 41-60 days. Vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) levels were higher in CSF samples obtained between days 0 and 20 than in CSF collected between days 41 and 60 of post-IVH. Concentrations of VCAM-1, intercellular adhesion molecule-1 (ICAM-1), and IL-8 strongly correlated with total heme levels in CSF. Applying the identified heme sources on human brain microvascular endothelial cells revealed that Hb oxidation products and free heme contribute to the inflammatory response. We concluded that RBC lysis, Hb oxidation, and heme release are important components of the inflammatory response in IVH. Pharmacological interventions targeting cell-free Hb, Hb oxidation products, and free heme could have potential to limit the neuroinflammatory response following IVH.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Immunology. - 11 (2020), p. 228. -
További szerzők:Tóth Andrea (1992-) (molekuláris biológus) Nagy Andrea (1958-) (csecsemő és gyermekgyógyász, neonatológus) Nyakundi, Benard Bogonko (1983-) (biokémikus) Fejes Zsolt (1988-) (molekuláris biológus) Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos) Novák László (1964-) (idegsebész) Bognár László (1958-) (idegsebész, gyermekidegsebész) Balogh Enikő (1987-) (molekuláris biológus) Paragh György (1953-) (belgyógyász) Kappelmayer János (1960-) (laboratóriumi szakorvos) Bácsi Attila (1967-) (immunológus) Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:GINOP-2.3.2-15-2016-00005
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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
Intézményi repozitóriumban (DEA) tárolt változat
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