title: Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation.
abstract: OBJECTIVE
  To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α (p38-MAPKα), Extra Cellular-Signal Regulated Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of type 1 diabetic pre-eclampsia, and the putative modulation of these indices by maternal vitamin C and E supplementation.
  
  
  METHODS
  Placental samples were obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy. Placenta from placebo-treated: normotensive (NT) [n=17], gestational hypertension (GH) [n=7] and pre-eclampsia (PE) [n=6] and vitamin-treated: NT (n=20), GH (n=4) and PE (n=3) was analysed. Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic activities of placental p38-MAPKα, ERK and JNK were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Nitrotyrosine immunostaining was present in placebo-treated NT, GH and PE placentae, with no significant difference observed between the groups. There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae. ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity.
  
  
  CONCLUSIONS
  Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and peroxynitrite production. Our results suggest that p38-MAPKα, ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation.
authors.affiliation: Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Johnston
authors.forename: L A
authors.initials: LA
authors.lastname: Powell
authors.forename: D R
authors.initials: DR
authors.lastname: McCance
authors.forename: K
authors.initials: K
authors.lastname: Pogue
authors.forename: C
authors.initials: C
authors.lastname: McMaster
authors.forename: S
authors.initials: S
authors.lastname: Gilchrist
authors.forename: V A
authors.initials: VA
authors.lastname: Holmes
authors.forename: I S
authors.initials: IS
authors.lastname: Young
authors.forename: A
authors.initials: A
authors.lastname: McGinty
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D019587:Dietary Supplements; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D009566:Nitrates / Q000378:metabolism*; D010919:Placebos; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D011254:Pregnancy in Diabetics / Q000188:drug therapy / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014443:Tyrosine / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D009566:Nitrates; D010919:Placebos; D011257:Pregnancy Proteins; D014815:Vitamins; D014443:Tyrosine; D048049:Extracellular Signal-Regulated MAP Kinases