Continuous inhibition of poly(ADP-ribose) polymerase does not reduce reperfusion injury in isolated rat heart.

Abstract

Poly(ADP-ribose) polymerase (PARP), an enzyme that is important to the regulation of nuclear function, is activated by DNA strand breakage. In massive DNA damage, PARP is overactivated, exhausting nicotinamide adenine dinucleotide and leading to cell death. Recent studies have succeeded in reducing cellular damage in ischemia/reperfusion by inhibiting PARP. However, PARP plays an important part in the DNA repair system, and its inhibition may be hazardous in certain situations. We compared the short-time inhibition of PARP against continuous inhibition during ischemia/reperfusion using isolated rat hearts. The hearts were reperfused after 21 minutes of ischemia with a bolus injection of 3-aminobenzamide (3-AB) (10 mg/kg) followed by continuous 3-AB infusion (50 μM) for the whole reperfusion period or for the first 6 minutes or without 3-AB. At the end of reperfusion, contractile function, high-energy phosphate content, nicotinamide adenine dinucleotide content, and infarcted area were significantly preserved in the 3-AB 6-minute group. In the 3-AB continuous group, these advantages were not apparent. At the end of reperfusion, PARP cleavage had significantly proceeded in the 3-AB continuous group, indicating initiation of the apoptotic cascade. Thus, continuous PARP inhibition by 3-AB does not reduce reperfusion injury in the isolated rat heart, which may be because of acceleration of apoptosis.

• Authors: Kenya Nishizawa, Shigeki Yanagida, Tadashi Yamagishi, Eiichi Takayama, Motoaki Bessho, Masatoshi Kusuhara, Takeshi Adachi, Fumitaka Ohsuzu
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 62 Issue 1 Pg. 99-105 (Jul 2013) ISSN: 1533-4023 [Electronic] United States
• PMID: 23846805 (Publication Type: Journal Article)

Chemical References

• Benzamides
• Cardiotonic Agents
• Enzyme Inhibitors
• Poly(ADP-ribose) Polymerase Inhibitors
• Sodium Radioisotopes
• Phosphocreatine
• NAD
• Phosphorus
• 3-aminobenzamide
• Sodium
• Poly(ADP-ribose) Polymerases
• Oncogene Protein v-akt

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Benzamides (therapeutic use)
• Blotting, Western
• Cardiotonic Agents (therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• In Vitro Techniques
• Magnetic Resonance Spectroscopy
• Male
• Myocardial Infarction (pathology)
• Myocardial Reperfusion Injury (prevention & control)
• Myocardium (enzymology)
• NAD (metabolism)
• Oncogene Protein v-akt (metabolism)
• Phosphocreatine (metabolism)
• Phosphorus (metabolism)
• Phosphorylation
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (metabolism)
• Rats
• Rats, Wistar
• Sodium (metabolism)
• Sodium Radioisotopes
• Treatment Failure
• Ventricular Function, Left (physiology)