Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia

Webster, Rose P.; Brockman, Diane E.; Myatt, L.

doi:10.1093/molehr/gal071

Cited by 54 publications

(38 citation statements)

References 72 publications

(71 reference statements)

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“…Furthermore, our results show that such impairment in HELLP syndrome is greater than what can be extrapolated from the literature in preeclampsia. Compared with the results by Webster et al (2006), who observed a roughly 50% reduction of phospho-p38 MAPK, our findings show about 80% reduction compared to controls, this means a more severe impairment in HELLP syndrome than preeclampsia.…”

Section: Discussioncontrasting

confidence: 83%

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The role of p38α mitogen-activated protein kinase gene in the HELLP syndrome

Corradetti

Saccucci

Emanuelli

et al. 2010

Cell Stress and Chaperones

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Mitogen-activated protein kinase (MAPK) p38α was shown to be implicated in the organogenesis of the placenta, and such placental alteration is crucial for the development of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. We aimed to analyze for the first time human placental expression of MAPK p38α in pregnancies complicated by HELLP. The placental expression of MAPK p38α was investigated by semiquantitative polymerase chain reaction using cDNA extracted from placental tissue of 15 pregnancies with HELLP syndrome and 15 gestational age-matched controls. Seven patients with HELLP also had intrauterine fetal growth restriction (IUGR). In placenta from pregnancy complicated by HELLP, the expression of MAPK p38α is significantly decreased compared to the group with normal pregnancy (p<0.001), while no difference was found between the HELLP and HELLP with IUGR subpopulations. Our study shows for the first time that MAPK p38α is expressed in the human placenta. Pregnancies with placental dysfunction and hypertensive complications are characterized by a significantly decreased expression of MAPK p38α. Our observations suggest that p38 MAPK signaling may be essential in placental angiogenesis and functioning.

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Section: Discussioncontrasting

confidence: 83%

“…We preferred to specifically focus our research on the HELLP syndrome, rather than preeclampsia, given that MAPK had been recently and extensively investigated in preeclamptic patients under different conditions both in vivo (Webster et al 2006) and in vitro (Cindrova-Davies et al 2007). …”

Section: Introductionmentioning

confidence: 99%

The role of p38α mitogen-activated protein kinase gene in the HELLP syndrome

Corradetti

Saccucci

Emanuelli

et al. 2010

Cell Stress and Chaperones

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“…Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been associated with pre-eclampsia (46,57,74). Mitochondrial mass (mitochondria being major sources of ROS/RNS) is increased in pre-eclamptic placentas (72).…”

mentioning

confidence: 99%

Nitroso-Redox Balance and Mitochondrial Homeostasis Are Regulated bySTOX1, a Pre-Eclampsia-Associated Gene

Doridot

Châtre²,

Ducat³

et al. 2014

Antioxidants & Redox Signaling

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Aims: Storkhead box 1 (STOX1) is a winged-helix transcription factor that is implicated in the genetic forms of a high-prevalence human gestational disease, pre-eclampsia. STOX1 overexpression confers pre-eclampsia-like transcriptomic features to trophoblastic cell lines and pre-eclampsia symptoms to pregnant mice. The aim of this work was to evaluate the impact of STOX1 on free radical equilibrium and mitochondrial function, both in vitro and in vivo. Results: Transcriptome analysis of STOX1-transgenic versus nontransgenic placentas at 16.5 days of gestation revealed alterations of mitochondria-related pathways. Placentas overexpressing STOX1 displayed altered mitochondrial mass and were severely biased toward protein nitration, indicating nitrosoredox imbalance in vivo. Trophoblast cells overexpressing STOX1 displayed an increased mitochondrial activity at 20% O 2 and in hypoxia, despite reduction of the mitochondrial mass in the former. STOX1 overexpression is, therefore, associated with hyperactive mitochondria, resulting in increased free radical production. Moreover, nitric oxide (NO) production pathways were activated, resulting in peroxynitrite formation. At low oxygen pressure, STOX1 overexpression switched the free radical balance from reactive oxygen species (ROS) to reactive nitrogen species (RNS) in the placenta as well as in a trophoblast cell line. Innovation: In pre-eclamptic placentas, NO interacts with ROS and generates peroxynitrite and nitrated proteins as end products. This process will deprive the maternal organism of NO, a crucial vasodilator molecule. Conclusion: Our data posit STOX1 as a genetic switch in the ROS/RNS balance and suggest an explanation for elevated blood pressure in pre-eclampsia. Antioxid. Redox Signal. 21, 819-834.

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“…MAPK (Webster et al, 2006). Thus, it is conceivable that inhibition of p38MAPK activity might contribute to attenuation of syncytin-2 expression, a hypothesis that requires further investigation.…”

mentioning

confidence: 99%

Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line

Delidaki

Hein

et al. 2011

Molecular and Cellular Endocrinology

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. Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line. Molecular and Cellular Endocrinology, Elsevier, 2010, 332 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 32A c c e p t e d M a n u s c r i p t respectively) the transcription factors old astrocyte specifically-induced substance (OASIS) and glial cells missing a (GCMa) (by 3 and 6 fold, respectively) and the syncytin-2 receptor, major facilitator superfamily domain containing 2 (MFSD2) (by 2 fold). Up-regulation of AKAP79 and AKAP250, (by 2.5 and 4 fold, respectively) was also identified in forskolin-treated BeWo cells. Forskolin effects on all these genes were suppressed by chemical inhibition of p38MAPK whereas only specific genes were sensitive to ERK1/2 inhibition. This data provide novel insights into the signalling molecules and mechanisms regulating fusogenic gene expression by the adenylyl cyclase pathway.

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Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia

Cited by 54 publications

References 72 publications

The role of p38α mitogen-activated protein kinase gene in the HELLP syndrome

The role of p38α mitogen-activated protein kinase gene in the HELLP syndrome

Nitroso-Redox Balance and Mitochondrial Homeostasis Are Regulated bySTOX1, a Pre-Eclampsia-Associated Gene

Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line

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