Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis

Wang,Juan; Hao,Lin; Wang,Yan; Qin,Weidong; Wang,Xin; Zhao,Tong; Liu,Yusheng; Sheng,Lin; Du,Yimeng; Zhang,Mengyuan; Lu,Qinghua

doi:10.3892/mmr.2014.2977

Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis

Authors:
- Juan Wang
- Lin Hao
- Yan Wang
- Weidong Qin
- Xin Wang
- Tong Zhao
- Yusheng Liu
- Lin Sheng
- Yimeng Du
- Mengyuan Zhang
- Qinghua Lu
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Affiliations: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Anesthesiology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250062, P.R. China, Department of Intensive Care Unit, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: November 19, 2014 https://doi.org/10.3892/mmr.2014.2977
Pages: 1768-1776
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Myocardial infarction (MI) is defined as the deprivation of the myocardial tissue of oxygen and nutrients, resulting in the induction of inflammation and apoptosis of the cardiomyocytes. Poly (ADP‑ribose) polymerase 1 (PARP1) is a nuclear enzyme closely associated with MI, that can be activated by DNA damage. Inducible nitric oxide synthase (iNOS) is a critical enzyme among the inflammatory cytokines. The present study aimed to investigate the underlying mechanism of the protective effects of PARP1 and iNOS inhibitor against MI, in rats. A total of 40 male Wistar rats were divided into four groups. The rats were anesthetized with sodium pentobarbital (50 mg/kg), and the left anterior descending coronary artery was occluded by ligation, using a 6‑0 polypropylene monofilament suture, at the left atrial apex, in order to induce MI. The rats from each group received an abdominal injection of either dimethylsulfoxide (100 µl, for MI group); PARP‑1 inhibitor, 3,4‑dihydro‑5‑[4‑(1‑piperidinyl)butoxy]‑1(2H)‑ isoquinolinone (DPQ; 10 mg/kg); or iNOS inhibitor, N‑(1‑naphthyl)ethylenediamine dihydrochloride (1400W; 10 mg/kg). The hearts were harvested from the rats after four weeks. Inhibition of PARP and iNOS activity improved heart function, as determined by serial echocardiography. The rate of apoptosis, as determined by a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, was reduced by 39.71 and 39.00% in the DPQ and 1400W groups, respectively, and this was accompanied by the downregulated expression of cleaved caspase‑3 and PARP1. Effective inhibition of PARP and iNOS, by DPQ and 1400W, was detected by western blotting and immunofluorescence, and was shown to repress O2‑ and nitrotyrosine levels, following MI. The present study confirmed that inhibition of PARP1 and iNOS was able to protect against ischemic myocardial damage, by reducing the levels of apoptosis.

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