Oxidative modification of lipoproteins by heme proteins: Promotion of oxidation and induction of cytoprotectants in vascular endothelial cells  Page description

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Details of project

  
Identifier
37883
Type K
Principal investigator Balla, József
Title in Hungarian Hem-fehérjék okozta lipoprotein modifikációk: Oxidatív vascularis károsodások kialakulása és az endothelialis adaptáció indukciója
Title in English Oxidative modification of lipoproteins by heme proteins: Promotion of oxidation and induction of cytoprotectants in vascular endothelial cells
Panel Cellular and Developmental Biology
Department or equivalent Institute of Internal Medicine (University of Debrecen)
Participants Balla, György
Varga, Zsuzsa
Starting date 2002-01-01
Closing date 2005-12-31
Funding (in million HUF) 13.805
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
Számos vaszkuláris megbetegedésben a hem-vas eredetű endotheliális károsodás pathogenetikai szerepére egyre több adat utal. Munkánk során in vitro és in vivo körülmények között (humán hem oxigenáz-1 deficienciában) igazoltuk, hogy a hem-protein eredetű hem, amellett hogy önmagában is citotoxikus, az LDL oxidatív modifikációja révén is vezethet endotheliális funkciózavarhoz. Endotheliális sejtkárosodás végstádiumú veseelégtelenségben szenvedőkben is igazolást nyert. Munkánk során bizonyítottuk, hogy a hemodialízis során az antioxidáns tulajdonságú retenciós molekulák eltávolítása elősegítheti az LDL oxidatív modifikációját és a bekövetkező endothelsejt-károsodás veszélyeztetheti az érrendszert. Az endothelium gyorsan változó oxidatív környezete és a késlekedő adaptáció megnövelheti az atherosclerosis rizikóját a hemodializált krónikus veseelégtelenségben szenvedő betegekben. A hem okozta érkárosodások vizsgálata mellett klinikai tanulmányban igazoltuk, hogy az agyi erek korai érelmeszesedésének rizikója elsősorban az inflammációs markerek megemelkedett szintjével van összefüggésben.
Results in English
Numerous pathologies may involve toxic side effects of free heme and heme derived iron. Deficinecy of the heme catabolizing enzyme, heme oxygenase-1 in both human and mice leads to abundance of circulating heme and damage to vascular endothelium. Although heme can be directly cytotoxic, we have shown that hemoglobin-derived heme might be indirectly cytotoxic through the generation of oxidized forms of low-density lipoprotein. Endothelial dysfunction has been observed in patients with chronic kidney disease on maintenance hemodialysis too. We have shown that oxidative modification of LDL and consequent endothelial cell damage is a result of depletion of retention solutes with antioxidant capacity, and might represent an immediate threat to the vasculature. The adaptation to such an insult may require many hours in order to gain defense mechanisms, leaving cells susceptible to oxidative damage. In a rapidly undulating oxidative environment of endothelium, the delayed adaptation may not be entirely sufficient to prevent lipid peroxidation and endothelial cell injury in uremic patients on hemodialysis, resulting in an enhanced risk for atherosclerosis.
Full text http://real.mtak.hu/389/
Decision
Yes





 

List of publications

  
Ujhelyi L, Balla G, Jeney V, Varga Z, Nagy E, Vercellotti GM, Agarwal A, Eaton JW, Balla J.: Hemodialysis reduces inhibitory effect of plasma ultrafiltrate on LDL oxidation and subsequent endothelial reactions., Kidney Int. 2006 Jan;69(1):144-51., 2006
Nagy E, Jeney V, Yachie A, Szabo RP, Wagner O, Vercellotti GM, Eaton JW, Balla G, Balla J.: Oxidation of hemoglobin by lipid hydroperoxide associated with low-density lipoprotein (LDL) and increased cytotoxic effect by LDL oxidation in heme oxygenase-1 (HO-1) de, Cell Mol Biol, 2005
Balla J, Vercellotti GM, Jeney V, Yachie A, Nagy E, Eaton JW, Balla G.: Heme, heme oxygenase and ferritin in vascular endothelial cell injury., Heme Oxygenase in Biology and Human Diseases, Leo Otterbein (ed). Nova Science, 2005
Smrzova J, Balla J, Bárány P: Inflammation and resistance to erythropoiesis-stimulating agents– what do we know and what needs to be clarified?, Nephrol Dial Transplant, 2005
Bak I, Szendrei L, Turoczi T, Papp G, Joo F, Das DK, de Leiris J, Der P, Juhasz B, Varga E, Bacskay I, Balla J, Kovacs P, Tosaki A: Heme oxygenase-1-related carbon monoxide production and ventricular fibrillation in isolated ischemic/reperfused mouse myocardium., FASEB J, 2003
Bereczki D, Emőke N, Pál A, Magyar MT, Balla J: Should soluble CD40 ligand be measured from serum or plasma samples., Arterioscler Thromb Vasc Biol, 2003
Balla J, Vercellotti GM, Nath K, Yachie A, Nagy E, Eaton J, JW, Balla G: Heme, heme oxygenase and ferritin in vascular endothelial cell injury., Nephrol Dial Transplant, 2003
Magyar TM, Szikszai Z, Balla J, Valikovics A, Kappelmayer J, Imre S, Balla G, Viktória J, Csiba L, Bereczki D: Early-onset carotid atherosclerosis is associated with increased intima-media thickness and elevated serum levels of inflammatory markers., Stroke, 2003
Balla J, Jeney V, Yachie A, Varga Z, Vercellotti GM, Eaton JW, Balla G: Pro-oxidant and cytotoxic effects of circulating heme., Blood, 2002
Bereczki D, Csipo I, Gyimesi E, Magyar TM, Valikovics A, Balla J, Sipka S: Inflammatory markers in patients with early onset occlusive carotid artery disease., Stroke, 2004
Magyar T, Valikovics F, Nagy D, Barna E, Csiba L, Bereczki D, Balla J, Blaskó G: Platelet derived CD40 ligand but not soluble CD40 levels are increased in early onset occlusive carotid artery disease., Stroke, 2004
Balla J, Jeney V, Yachie A, Vercellotti GM, Eaton JW, Balla G: Balla J, Jeney V, Yachie A, Vercellotti GM, Eaton JW, Balla G, Heme Oxygenase: Regulation, Function and Clinical Application Conference. Uppsala, Sweden, 2003
Marinho M, Vasilevskaya T, Tokaji L, Gregoire C, Balla J, Soares MP: Generation and characterization of on engendered form of heme oxygenase-1 that can enter cells spontaneously., Heme Oxygenase: Regulation, Function and Clinical Application Conference. Uppsala, Sweden, 2003
Bereczki D, Balla J, Magyar T, Pal A, Nagy E, Barna E, Csiba L, Blaskó G: Serum level of the soluble CD40 ligand are increased in young patients with carotid atherosclerosis, European Journal of Neurology, 2003
Valikovics A, Balla J, Magyar T, Szikszai Z, Imres S, Csiba L, Balla G, Kappelmayer J, Bereczki D: Serum homocysteine and c-reactive protein are higher in young patients with occlusive carotid artery disease, Cerebrovasc dis, 2003
Balla J: Possible role of heme oxygenase-1 and ferritin in the pathogenesis of vasculitis., 16th Danube Symposium on Nephrology, 2002
Ujhelyi L, Jeney V, Dobolyi A, Varga Z, Kakuk G, Balla G, Balla J: Oxidative resistance of low-density lipoprotein is changing during hemodialysis., Nephrol Dial Transplant, 2002
Balla J, Vercellotti GM, Jeney V, Yachie A, Nagy E, Eaton JW, Balla G.: Heme, heme oxygenase and ferritin in vascular endothelial cell injury., Mol Nutr Food Res. 2005 Nov;49(11):1030-43., 2005
Vas T, Wagner Z, Jenei V, Varga Z, Kovacs T, Wittmann I, Schinzel R, Balla G, Balla J, Heidland A, Nagy J.: Oxidative stress and non-enzymatic glycation in IgA nephropathy, Clin Nephrol. 2005 Nov;64(5):343-51, 2005
Balla J, Vercellotti GM, Jeney V, Yachie A, Nagy E, Eaton JW, Balla G.: Heme, heme oxygenase and ferritin in vascular endothelial cell injury., Heme Oxygenase in Biology and Human Diseases, Leo Otterbein (ed). Nova Science, 2005




 

Events of the project

  
2012-07-24 09:48:38
Kutatóhely váltás
A kutatás helye megváltozott. Korábbi kutatóhely: ÁOK Belgyógyászati Intézet, I. sz. Belgyógyászati Klinika (Debreceni Egyetem), Új kutatóhely: ÁOK Belgyógyászati Intézet (Debreceni Egyetem).



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