Abstract Objective: Mitogen-activated protein kinase (MAPK) signal transduction pathways regulate various genes which have been implicated in the pathophysiology of preeclampsia and the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. We therefore investigated whether the activity of the three MAPKs - Jun aminoterminal kinase (Jnk), extracellular regulated kinase (Erk) and p38 - is altered in placental tissue of women with preeclampsia and HELLP synfrome. Methods: Placental activity (immunoprecipitation-kinase assay) and protein expression (Western blot) of Jnk-, Erk- and p38-MAPK was measured in four groups of eight women each, with preeclampsia, HELLP syndrome, normal vaginal and cesarean delivery. To further characterise the Jnk signal transduction pathway - phosphorylation of c-Jun - a downstream effector of Jnk-MAPK was analysed by Western blotting and the activity of Rac1 - an upstream activator of the Jnk signalling pathways - was determined by a pull-down assay. Results: The activity of Jnk-MAPK was significantly reduced in placentas obtained from women with preeclampsia or HELLP syndrome compared to those with normal vaginal or cesarean delivery, while the level of Jnk protein expression was similar. Phosphorylation of the transcription factor c-Jun as well as Rac1 activity was also significantly lower in the preeclampsia and HELLP cases than in the control groups. p38-MAPK activity was significantly higher in preeclampsia than in HELLP syndrome. There was no change in Erk activity or protein expression between subgroups. Conclusion: In placentas of patients with preeclampsia or HELLP syndrome a Rac1/Jnk/c-Jun-dependent signal transduction pathway is down-regulated.     «

Abstract Objective: Mitogen-activated protein kinase (MAPK) signal transduction pathways regulate various genes which have been implicated in the pathophysiology of preeclampsia and the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. We therefore investigated whether the activity of the three MAPKs - Jun aminoterminal kinase (Jnk), extracellular regulated kinase (Erk) and p38 - is altered in placental tissue of women with preeclampsia and HELLP synfrome. Methods: Placental act...     »