Mol. Hum. Reprod. Advance Access originally published online on September 2, 2006
Molecular Human Reproduction 2006 12(11):677-685; doi:10.1093/molehr/gal071
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Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia
1Department of Obstetrics and Gynecology and 2Department of Molecular and Cellular Physiology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, University of Cincinnati, College of Medicine, PO Box 670526, Cincinnati, OH 45267-0526, USA. E-mail: rose.webster{at}uc.edu
Peroxynitrite, a potent pro-oxidant formed from the interaction of superoxide and nitric oxide, has been widely reported to be nitrating tyrosine residues in proteins resulting in the formation of nitrotyrosine. Biological nitration of tyrosine, a footprint of oxidative injury, has been found to occur in various pathological states including pre-eclampsia, a leading cause of maternal mortality and increased perinatal mortality. Oxidative stress is a major contributor to endothelial dysfunction in pre-eclampsia. Previously, we have demonstrated increased nitrotyrosine immunostaining in placental villous vascular endothelium, surrounding vascular smooth muscle and villous stroma from pre-eclamptic or diabetic pregnancies. Immunoprecipitation (IP) with antinitrotyrosine antibodies followed by immunoblot analysis identified increased nitration of phospho-p38 mitogen-activated protein kinase (MAPK) in the pre-eclamptic placenta. The catalytic activity of p38 MAPK and concentration of phospho-p38 MAPK was also found to be reduced in placentae from pre-eclamptic pregnancies. Comparison of peptide masses of a 42-kDa protein obtained by mass spectrometry with masses of a theoretical tryptic digest of p38 MAPK that was modified by phosphorylation and nitration identified the protein to be p38 MAPK.
Key words: nitration/nitrotyrosine/p38 MAPK/peroxynitrite/pre-eclampsia
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