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Threshold of peroxynitrite cytotoxicity in bovine pulmonary artery endothelial and smooth muscle cells

Agbani, Ejaife and Coats, Paul and Wadsworth, Roger (2011) Threshold of peroxynitrite cytotoxicity in bovine pulmonary artery endothelial and smooth muscle cells. Toxicology in Vitro, 25 (8). 1680–1686. ISSN 0887-2333

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Abstract

Peroxynitrite is widely reported as highly cytotoxic; yet recent evidence indicates that at certain concentrations, it can induce pulmonary cell hyper-proliferation and tissue remodelling. This study aimed to establish the threshold concentration of peroxynitrite to induce functional impairment of bovine pulmonary artery endothelial (PAEC) and smooth muscle cells (PASMC). PAEC or PASMC were exposed to solution of peroxynitrite or 3-morpholinosydnonimine (SIN-1). Twenty-four hour cell viability, DNA synthesis, and protein biochemistry were assessed by trypan blue dye exclusion, [(3)H] thymidine incorporation and western blot analysis, respectively. Threshold concentration of peroxynitrite to significantly impair viability of PAEC and PASMC was 2μM peroxynitrite. In PASMC and PAEC, low concentrations of peroxynitrite (2nM-0.2μM) increased cell proliferation and did not activate p38 MAP kinase. The decrease in DNA synthesis and cell viability caused by 2μM peroxynitrite was associated with caspase-3 cleavage but not p38 activation. Also, 2-20μM peroxynitrite significantly activated poly ADP ribose polymerase and stress activated kinase JNK in PAEC. However, the higher concentration of 20μM peroxynitrite did cause a threefold increase in p38 activation. In conclusion, the threshold for the cytotoxic effects of peroxynitrite was 2μM; which caused apoptotic cell death independent of p38 MAP kinase activation in pulmonary artery cells.

Item type: Article
ID code: 35460
Keywords: peroxynitrite, cytotoxicity, pulmonary endothelial cells, smooth muscle cells, Pharmacy and materia medica, Toxicology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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Depositing user: Pure Administrator
Date Deposited: 31 Oct 2011 15:48
Last modified: 05 Sep 2014 13:14
URI: http://strathprints.strath.ac.uk/id/eprint/35460

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