Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 677-685 |
| Number of pages | 9 |
| Journal | Molecular Human Reproduction |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2006 |
| Externally published | Yes |
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Keywords
- Nitration
- Nitrotyrosine
- p38 MAPK
- Peroxynitrite
- Pre-eclampsia
ASJC Scopus subject areas
- Obstetrics and Gynecology
- Genetics
- Developmental Biology
- Embryology
- Cell Biology
Cite this
Nitration of p38 MAPK in the placenta : Association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia. / Webster, Rose P.; Brockman, D.; Myatt, Leslie.
In: Molecular Human Reproduction, Vol. 12, No. 11, 11.2006, p. 677-685.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitration of p38 MAPK in the placenta
T2 - Association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia
AU - Webster, Rose P.
AU - Brockman, D.
AU - Myatt, Leslie
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Nitration
KW - Nitrotyrosine
KW - p38 MAPK
KW - Peroxynitrite
KW - Pre-eclampsia
UR - http://www.scopus.com/inward/record.url?scp=33750223130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750223130&partnerID=8YFLogxK
U2 - 10.1093/molehr/gal071
DO - 10.1093/molehr/gal071
M3 - Article
C2 - 16951426
AN - SCOPUS:33750223130
VL - 12
SP - 677
EP - 685
JO - Molecular Human Reproduction
JF - Molecular Human Reproduction
SN - 1360-9947
IS - 11
ER -