Abstract
Nitric oxide synthase (NOS)-2 is expressed during acute cardiac allograft rejection in association with death of heart muscle cells. The nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) synthase (PARS) is activated by agonists such as NO and peroxynitrite, which cause single-strand DNA breaks; PARS, in turn can promote both necrosis and apoptosis. To investigate the hypothesis that NO produced by NOS-2 in cardiomyocytes activates PARS and contributes to heart muscle cell death by apoptosis, experiments were performed using a heterotopic rat abdominal heart transplant model and cytokine-stimulated heart muscle cells in tissue culture. Cardiac allografts were treated after transplantation with either the PARS inhibitor 5-aminoisoquinolinone at 3 mg/kg subcutaneously daily or with vehicle. Isolated purified adult rat cardiomyocytes incubated with cytokines to induce NOS-2 were treated in vitro with another PARS inhibitor, 3-aminobenzamide (3AB). PARS inhibition increased cardiac-allograft survival from 6 +/- 2 to 10 +/- 3 days (n=6, n=6, P<0.05). The inflammatory infiltrate, NOS-2-positive macrophages, myocyte apoptosis, and myocyte content of nitrotyrosine and poly(ADP-ribose) were significantly decreased in PARS inhibited...Continue Reading
References
Aug 1, 1994·The Journal of Clinical Investigation·X YangP J Cannon
Jan 1, 1995·The Journal of Experimental Medicine·N K WorrallT B Ferguson
Feb 1, 1995·The Journal of Clinical Investigation·D J PinskyP J Cannon
Oct 1, 1996·Circulation·M SzabolcsP J Cannon
Jan 1, 1996·Free Radical Biology & Medicine·C Szabó
Nov 1, 1996·The American Journal of Physiology·J S Beckman, W H Koppenol
Sep 23, 1997·Journal of Molecular and Cellular Cardiology·E GiladC Szabó
Feb 17, 1998·Cardiovascular Research·B ZingarelliC Szabó
Apr 16, 1998·Transplantation·M J SzabolcsP J Cannon
Jun 9, 1998·Shock·C Szabó
Jan 23, 1999·Circulation Research·D J IngN H Bishopric
Feb 17, 1999·Circulation·J KoglinM E Russell
Jun 24, 2000·British Journal of Pharmacology·M C McDonaldC Thiemermann
May 23, 2001·Circulation·M J SzabolcsP J Cannon
Nov 8, 2001·European Journal of Pharmacology·N WaymanC Thiemermann
Feb 19, 2002·Oncogene·M Teresa ValenzuelaF Javier Oliver
Oct 31, 2002·Circulation·Matthias J SzabolcsPaul J Cannon
Dec 20, 2002·Transplantation·Ningsheng MaPaul J Cannon
Aug 5, 2003·Journal of Cellular Biochemistry·Józefa Wesierska-GadekGerald Schmid
Citations
Feb 2, 2013·Molecular Aspects of Medicine·Nicola J Curtin, Csaba Szabo
Mar 11, 2008·Antioxidants & Redox Signaling·Galen M PieperChristopher P Johnson
Oct 28, 2008·Biochemical and Biophysical Research Communications·Dirk M MaybauerDaniel L Traber
Jul 19, 2008·Free Radical Biology & Medicine·Jeannette Vásquez-VivarGalen M Pieper
Jun 15, 2006·Transplant International : Official Journal of the European Society for Organ Transplantation·Gábor SzabóSiegfried Hagl
Jul 5, 2006·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Gábor SzabóThomas J Dengler
Feb 23, 2008·Free Radical Biology & Medicine·Galen M Pieper, Allan M Roza
Aug 15, 2017·British Journal of Pharmacology·Sevil Korkmaz-IcözGábor Szabó
Jan 2, 2009·Journal of Medicinal Chemistry·Anna-Marie LordMichael D Threadgill