title: Poly(ADP-ribose) polymerase activation and cell injury in the course of rat heart heterotopic transplantation.
abstract: Free radicals and other reactive species generated during reperfusion of ischemic tissues may cause DNA damage and, consequently, the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP). An excessive PARP activation may result in a depletion of intracellular NAD+ and ATP, hence cell suffering and, ultimately, cell death. The present study is aimed at clarifying the role of PARP in a heart transplantation procedure and the contribution of myocyte necrosis and/or apoptosis to this process. In our experimental model, rat heart subjected to heterotopic transplantation, low temperature global ischemia (2 h) was followed by an in vivo reperfusion (30 or 60 min). Under these conditions clear signs of oxidative stress, such as lipoperoxidation and DNA strand breaks, were evident. In addition to a marked activation, accompanied by a significant NAD+ and ATP depletion, PARP protein levels significantly increased after 60 min of reperfusion. Ultrastructural analysis showed nuclear clearings, intracellular oedema and plasma membrane discontinuity. Other relevant observations were the absence of typical signs of apoptosis like caspase-3 activation and PARP cleavage, random DNA fragmentation, rise in serum levels of heart damage markers. Our results suggest that during heart transplantation, the activation of PARP, causing energy depletion, results in myocardial cell injury whose dominant feature, at least in our experimental model, is necrosis rather than apoptosis.
authors: Dipartimento di Scienze Biochimiche, Università di Firenze, Italy.
authors: Claudia
authors: C
authors: Fiorillo
authors: Stefania
authors: S
authors: Pace
authors: Vanessa
authors: V
authors: Ponziani
authors: Chiara
authors: C
authors: Nediani
authors: Avio Maria
authors: AM
authors: Perna
authors: Piero
authors: P
authors: Liguori
authors: Cristina
authors: C
authors: Cecchi
authors: Niccolò
authors: N
authors: Nassi
authors: Gian Paolo
authors: GP
authors: Donzelli
authors: Lucia
authors: L
authors: Formigli
authors: Paolo
authors: P
authors: Nassi
mesh_terms: D000225:Adenine / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D016027:Heart Transplantation; D015227:Lipid Peroxidation; D009206:Myocardium / Q000648:ultrastructure; D009336:Necrosis; D018384:Oxidative Stress; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D013997:Time Factors; D014682:Vena Cava, Inferior / Q000378:metabolism
chemical_list: D011065:Poly(ADP-ribose) Polymerases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000225:Adenine