A poli (ADP-ribóz) polimeráz enzim szerepe diabeteszes komplikációk patogenezisében
Title in English
Poly (ADP-ribose) polymerase and diabetic complications
Panel
Physiology, Pathophysiology, Pharmacology and Endocrinology
Department or equivalent
Cell Screen Applied Research Center (Semmelweis University)
Participants
Csapó, Zsolt Kiss, András Rosivall, László
Starting date
2004-01-01
Closing date
2007-12-31
Funding (in million HUF)
6.037
FTE (full time equivalent)
0.00
state
closed project
Final report
Results in Hungarian
A jelen munkában a PARP fehérje szerepét vizsgáltuk a cukobetegség szövôdményeinek kialakulásában. Kimutattuk, hogy az erek és a vese károsodásában fontos szerepe van ennek a fehérjének, és a fehérje aktivitásának gátlása állatokban javítja a betegség lefolyását. Összefüggést találtunk a PARP aktivációja, valamint a rosszul beállított cukorbetegség között, és kimutattuk különféle sejten belüli szignál transzdukciós út szerepét ezekben a folyamatokban. A munka számos nemzetközi szintû közleményt eredményezett.
Results in English
In the present project, we have investigated the role of the PARP enzyme in the pathogenesis of diabetic complications. We have demonstrated that the vascular and renal damage associated with diabetes is importantly mediated by the activation of the PARP enzyme. We have demonstrated a relationship between poorly controlled diabetes and the activation of PARP and we have demonstrated the role of several intracellular signal transduction pathways in the process. The work has resulted in a number of internationally significant publications.
Xiao CY, Chen M, Zsengellér Z, Szabó C: Poly(ADP-ribose) polymerase contributes to the development of myocardial infarction in diabetic rats and regulates the translocation of apopotosis-inducing factor, J Pharmacol Exp Ther, 310: 498-504, 2004
Szabo C.: Roles of poly(ADP-ribose) polymerase activation in the pathogenesis of diabetes mellitus and its complications., Pharmacol Res. 2005 Jul;52(1):60-71., 2005
Pacher P, Szabo C.: Role of poly(ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme., Antioxid Redox Signal. Nov-Dec;7(11-12):1568-80., 2005
Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabo C, Ceriello A.: Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) p, J Thromb Haemost. 2004 Aug;2(8):1453-9., 2004
Kiss L, Szabo C.: The pathogenesis of diabetic complications: the role of DNA injury and poly(ADP-ribose) polymerase activation in peroxynitrite-mediated cytotoxicity., Mem Inst Oswaldo Cruz. Mar;100 Suppl 1:29-37., 2005
op den Buijs J, Miklos Z, van Riel NA, Prestia CM, Szenczi O, Toth A, Van der Vusse GJ, Szabo C, Ligeti L, Ivanics T.: beta-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes., Life Sci. 2005 Jan 21;76(10):1083-98., 2005
Pacher P, Obrosova IG, Mabley JG, Szabo C.: Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies., Curr Med Chem. 2005;12(3):267-75., 2005
Ligeti L, Szenczi O, Prestia CM, Szabo C, Horvath K, Marcsek ZL, van Stiphout RG, van Riel NA, Op den Buijs J, Van der Vusse GJ, Ivanics T.: Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy., Int J Mol Med. Jun;17(6):1035-43., 2006
Obrosova IG, Drel VR, Kumagai AK, Szabo C, Pacher P, Stevens MJ.: Early diabetes-induced biochemical changes in the retina: comparison of rat and mouse models., Diabetologia. Oct;49(10):2525-33., 2006
Pacher P, Szabo C.: Role of peroxynitrite in the pathogenesis of cardiovascular complications of diabetes., Curr Opin Pharmacol. Apr;6(2):136-41., 2006
Szabo C, Biser A, Benko R, Bottinger E, Susztak K.: Poly(ADP-ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Leprdb/db mice., Diabetes. Nov;55(11):3004-12, 2006
Horvath EM, Szabó C.: Poly(ADP-ribose) polymerase as a drug target for cardiovascular disease and cancer: an update., Drug News Perspect. 2007 Apr;20(3):171-81, 2007
Ihnat MA, Thorpe JE, Kamat CD, Szabó C, Green DE, Warnke LA, Lacza Z, Cselenyák A, Ross K, Shakir S, Piconi L, Kaltreider RC, Ceriello A.: Reactive oxygen species mediate a cellular 'memory' of high glucose stress signalling., Diabetologia. 2007 Jul;50(7):1523-31, 2007
