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001-es BibID:BIBFORM078592
Első szerző:Balla József (belgyógyász, nephrológus)
Cím:Role of heme in soft tissue mineralization / Balla József, Zarjou Abolfazl, Agarwal Anupam, Becs Gergely, Kovács Katalin, Nyitrai Mónika, Potor László, Pethő Dávid, Oros Melinda, Zavaczki Erzsébet, Arosio Paolo, Eaton John, Balla György
Dátum:2016
ISSN:0891-5849
Megjegyzések:Infiltration of red blood cells into atherosclerotic lesions is a common event in the progression of atherosclerosis. Recently we have observed that after infiltration and exposure of erythrocytes to plaque material, are lysed, and the liberated hemoglobin is oxidized to ferryl hemoglobin (FeIII/FeIV?O) and ferri (FeIII) hemoglobin. After oxidation of ferro (FeII) hemoglobin heme dissociates from globin then is translocated into resident cells including smooth muscle cells within arteries. Mounting evidence suggests an essential role for the heme oxygenase 1 (HO-1)/ferritin system to maintain homeostasis of vascular function. We examined whether induction of HO-1 and ferritin by heme alters mineralization of human smooth muscle cells provoked by phosphorous and vitamin D3 analogs. Upregulation of the HO-1/ferritin system inhibited human smooth muscle cells calcification and osteoblastic differentiation. Of the products of the system, only ferritin and, to a lesser extent, biliverdin were responsible for the inhibition. Ferritin heavy chain and ceruloplasmin, which both possess ferroxidase activity, inhibited calcification; a site-directed mutant of ferritin heavy chain, which lacked ferroxidase activity, failed to inhibit calcification. In addition, osteoblastic transformation of human smooth muscle cells (assessed by upregulation of core binding factor alpha-1, osteocalcin, and alkaline phosphatase activity) was diminished by ferritin/ferroxidase activity. Furthermore, iron-provoked inhibition of osteoblast activity was also demonstrated to be mediated by ferritin and its ferroxidase activity. We conclude that induction of the HO-1/ferritin system prevents calcification and osteoblastic differentiation of human smooth muscle cells mainly via the ferroxidase activity of ferritin.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
heme
mineralization
Megjelenés:Free Radical Biology And Medicine. - 96 (2016), p. S13. -
További szerzők:Zarjou, Abolfazl (1979-) (kutató orvos) Agarwal, Anupam Becs Gergely Sikura Katalin Éva (1985-) (biológus) Nyitrai Mónika Potor László Pethő Dávid Oros Melinda (1975-) (molekuláris biológus) Zavaczki Erzsébet (1983-) (biotechnológus) Arosio, Paolo Eaton, John W. Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus)
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2.

001-es BibID:BIBFORM078538
035-os BibID:(WoS)000513525100008 (Scopus)85067838371
Első szerző:Sikura Katalin Éva (biológus)
Cím:Hydrogen sulfide inhibits calcification of heart valves; implications for calcific aortic valve disease / Katalin Éva Sikura, László Potor, Tamás Szerafin, Melinda Oros, Péter Nagy, Gábor Méhes, Zoltán Hendrik, Abolfazl Zarjou, Anupam Agarwal, Niké Posta, Roberta Torregrossa, Matthew Whiteman, Ibolya Fürtös, György Balla, József Balla
Dátum:2020
ISSN:0007-1188
Megjegyzések:BACKGROUND AND PURPOSE: Calcification of heart valves is a frequent pathological finding in CKD patients and in elderly. Hydrogen sulfide (H2 S) has been suggested to possess various anti-calcific actions. We aimed to investigate H2 S as a potential therapeutic in valvular calcification and to identify its targets in the pathogenesis. EXPERIMENTAL APPROACH: Potential of H2 S for regulating osteoblastic transdifferentiation of valvular interstitial cells (VIC) isolated from human aortic valves were studied and tested for valvular calcification in apolipoprotein E-deficient mice (ApoE-/- ). KEY RESULTS: In human VIC H2 S treatment employing donors (NaSH, Na2 S, GYY4137, AP67, AP72) inhibited mineralization/osteoblastic transdifferentiation in a dose-responsive manner in response to phosphate. Accumulation of calcium in the extracellular matrix and expression of osteocalcin and alkaline phosphatase was abrogated. Nuclear translocation of the RUNX2 did not occur, and phosphate uptake was lowered. We also found that pyrophosphate generation was increased via up-regulating ENPP2 and ANK1. Lowering endogenous production of H2 S by concomitant silencing of CSE and CBS favored VIC calcification. IHC and Western blot analysis of human specimens revealed higher levels of CSE expression in aorta stenosis valves with calcification (AS) compared to valves of aorta insufficiency (AI). In contrast, tissue H2 S generation was lower in AS valves compared to AI valves. We observed an inhibition of valvular calcification by H2 S in ApoE-/- mouse on high-fat diet. CONCLUSION AND IMPLICATIONS: Our study suggests that the CSE-CBS/H2 S system exhibits an anti-calcification function in heart valves providing a novel therapeutic approach to prevent hardening of valves. This article is protected by copyright. All rights reserved. KEYWORDS: AP67; AP72; GYY4137; H2S; aortic valve; apolipoprotein E knockout mice; calcification; pyrophosphate
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
hydrogen sulphide
valvular calcification
Megjelenés:British Journal of Pharmacology. - 177 : 4 (2020), p. 793-809. -
További szerzők:Potor László Szerafin Tamás (1960-) (szívsebész, mellkassebész) Oros Melinda (1975-) (molekuláris biológus) Nagy Péter (1976-) (vegyész) Méhes Gábor (1966-) (patológus) Hendrik Zoltán (1986-) (orvos) Zarjou, Abolfazl (1979-) (kutató orvos) Agarwal, Anupam Posta Niké Torregrossa, Roberta Whiteman, Matthew Fürtös Ibolya Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Balla József (1959-) (belgyógyász, nephrológus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00043
GINOP
EFOP-3.6.2-16-2017-00006
EFOP
OTKA-112333
OTKA
11003
MTA
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3.

001-es BibID:BIBFORM076938
035-os BibID:(WoS)000460459200017 (Scopus)85062410676
Első szerző:Sikura Katalin Éva (biológus)
Cím:Potential Role of H-Ferritin in Mitigating Valvular Mineralization / Katalin Éva Sikura, László Potor, Tamás Szerafin, Abolfazl Zarjou, Anupam Agarwal, Paolo Arosio, Maura Poli, Zoltán Hendrik, Gábor Méhes, Melinda Oros, Niké Posta, Lívia Beke, Ibolya Fürtös, György Balla, József Balla
Dátum:2019
ISSN:1079-5642
Megjegyzések:Objective- Calcific aortic valve disease is a prominent finding in elderly and in patients with chronic kidney disease. We investigated the potential role of iron metabolism in the pathogenesis of calcific aortic valve disease. Approach and Results- Cultured valvular interstitial cells of stenotic aortic valve with calcification from patients undergoing valve replacement exhibited significant susceptibility to mineralization/osteoblastic transdifferentiation in response to phosphate. This process was abrogated by iron via induction of H-ferritin as reflected by lowering ALP and osteocalcin secretion and preventing extracellular calcium deposition. Cellular phosphate uptake and accumulation of lysosomal phosphate were decreased. Accordingly, expression of phosphate transporters Pit1 and Pit2 were repressed. Translocation of ferritin into lysosomes occurred with high phosphate-binding capacity. Importantly, ferritin reduced nuclear accumulation of RUNX2 (Runt-related transcription factor 2), and as a reciprocal effect, it enhanced nuclear localization of transcription factor Sox9 (SRY [sex-determining region Y]-box 9). Pyrophosphate generation was also increased via upregulation of ENPP2 (ectonucleotide pyrophosphatase/phosphodiesterase-2). 3H-1, 2-dithiole-3-thione mimicked these beneficial effects in valvular interstitial cell via induction of H-ferritin. Ferroxidase activity of H-ferritin was essential for this function, as ceruloplasmin exhibited similar inhibitory functions. Histological analysis of stenotic aortic valve revealed high expression of H-ferritin without iron accumulation and its relative dominance over ALP in noncalcified regions. Increased expression of H-ferritin accompanied by elevation of TNF-α (tumor necrosis factor-α) and IL-1β (interleukin-1β) levels, inducers of H-ferritin, corroborates the essential role of ferritin/ferroxidase via attenuating inflammation in calcific aortic valve disease. Conclusions- Our results indicate that H-ferritin is a stratagem in mitigating valvular mineralization/osteoblastic differentiation. Utilization of 3H-1, 2-dithiole-3-thione to induce ferritin expression may prove a novel therapeutic potential in valvular mineralization.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
arteriosclerosis
chronic kidney disease
phosphate
stenosis
vascular calcification
Megjelenés:Arteriosclerosis Thrombosis and Vascular Biology. - 39 : 3 (2019), p. 413-431. -
További szerzők:Potor László Szerafin Tamás (1960-) (szívsebész, mellkassebész) Zarjou, Abolfazl (1979-) (kutató orvos) Agarwal, Anupam Arosio, Paolo Poli, Maura Hendrik Zoltán (1986-) (orvos) Méhes Gábor (1966-) (patológus) Oros Melinda (1975-) (molekuláris biológus) Posta Niké Beke Lívia Fürtös Ibolya Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Balla József (1959-) (belgyógyász, nephrológus)
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4.

001-es BibID:BIBFORM020460
Első szerző:Zavaczki Erzsébet (biotechnológus)
Cím:Hydrogen sulfide inhibits the calcification and osteoblastic differentation of vascular smooth muscle cells / Erzsebet Zavaczki, Viktoria Jeney, Anupam Agarwal, Abolfazl Zarjou, Melinda Oros, Monika Katko, Zsuzsa Varga, Gyorgy Balla, Jozsef Balla
Dátum:2011
ISSN:0085-2538
Megjegyzések:Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is involved in the pathogenesis of vascular calcification. Hydrogen sulfide (H2S) is a gas endogenously produced by cystathionine gamma-lyase in VSMC. Here we determined whether H2S plays a role in phosphate-induced osteoblastic transformation and mineralization of VSMC. Hydrogen sulfide was found to inhibit calcium deposition in the extracellular matrix and to suppress the induction of the genes involved in osteoblastic transformation of VSMC: alkaline phosphatase, osteocalcin, and Cbfa1. Moreover, phosphate uptake and phosphate-triggered upregulation of the sodium-dependent phosphate cotransporter (Pit-1) were also prevented by H2S. Reduction of endogenous production of H2S by inhibition of cystathionine gamma-lyase activity resulted in increased osteoblastic transformation and mineralization. Low plasma levels of H2S, associated with decreased cystathionine gamma-lyase enzyme activity, were found in patients with chronic kidney disease receiving hemodialysis. Thus, H2S is a potent inhibitor of phosphate-induced calcification and osteoblastic differentiation of VSMC. This mechanism might contribute to accelerated vascular calcification in chronic kidney disease.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Kidney International. - 80 : 7 (2011), p. 731-739. -
További szerzők:Jeney Viktória (1971-) (vegyész, kémia tanár) Agarwal, Anupam Zarjou, Abolfazl (1979-) (kutató orvos) Oros Melinda (1975-) (molekuláris biológus) Katkó Mónika (1980-) (biológus) Varga Zsuzsa (1951-) (biokémikus, nephrológus) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Balla József (1959-) (belgyógyász, nephrológus)
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
A hem-stressz és a hemoxigenáz-ferritin-ferroxidáz rendszerek szerepe az erek szöveti kalcifikációjában
OTKA-K75883
OTKA
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