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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
  • View Affiliations / Copyright

    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
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1768-1776
    |
    Published online on: November 19, 2014
       https://doi.org/10.3892/mmr.2014.2977
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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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Copy and paste a formatted citation
Spandidos Publications style
Wang J, Hao L, Wang Y, Qin W, Wang X, Zhao T, Liu Y, Sheng L, Du Y, Zhang M, Zhang M, et al: Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis. Mol Med Rep 11: 1768-1776, 2015.
APA
Wang, J., Hao, L., Wang, Y., Qin, W., Wang, X., Zhao, T. ... Lu, Q. (2015). Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis. Molecular Medicine Reports, 11, 1768-1776. https://doi.org/10.3892/mmr.2014.2977
MLA
Wang, J., Hao, L., Wang, Y., Qin, W., Wang, X., Zhao, T., Liu, Y., Sheng, L., Du, Y., Zhang, M., Lu, Q."Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis". Molecular Medicine Reports 11.3 (2015): 1768-1776.
Chicago
Wang, J., Hao, L., Wang, Y., Qin, W., Wang, X., Zhao, T., Liu, Y., Sheng, L., Du, Y., Zhang, M., Lu, Q."Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis". Molecular Medicine Reports 11, no. 3 (2015): 1768-1776. https://doi.org/10.3892/mmr.2014.2977
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Hao L, Wang Y, Qin W, Wang X, Zhao T, Liu Y, Sheng L, Du Y, Zhang M, Zhang M, et al: Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis. Mol Med Rep 11: 1768-1776, 2015.
APA
Wang, J., Hao, L., Wang, Y., Qin, W., Wang, X., Zhao, T. ... Lu, Q. (2015). Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis. Molecular Medicine Reports, 11, 1768-1776. https://doi.org/10.3892/mmr.2014.2977
MLA
Wang, J., Hao, L., Wang, Y., Qin, W., Wang, X., Zhao, T., Liu, Y., Sheng, L., Du, Y., Zhang, M., Lu, Q."Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis". Molecular Medicine Reports 11.3 (2015): 1768-1776.
Chicago
Wang, J., Hao, L., Wang, Y., Qin, W., Wang, X., Zhao, T., Liu, Y., Sheng, L., Du, Y., Zhang, M., Lu, Q."Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis". Molecular Medicine Reports 11, no. 3 (2015): 1768-1776. https://doi.org/10.3892/mmr.2014.2977
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