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 (https://doi.org/10.1016/j.tiv.2011.07.005)
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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.
ORCID iDs
Agbani, Ejaife, Coats, Paul ORCID: https://orcid.org/0000-0002-6035-675X and Wadsworth, Roger;-
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Item type: Article ID code: 35460 Dates: DateEventDecember 2011Published18 July 2011Published OnlineSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 31 Oct 2011 15:48 Last modified: 11 Nov 2024 09:58 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/35460