Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation

• Published in: Journal of diabetes and its complications 2013-07, Vol.27 (4), p.322-327
• Main Authors: Johnston, P.C, Powell, L.A, McCance, D.R, Pogue, K, McMaster, C, Gilchrist, S, Holmes, V.A, Young, I.S, McGinty, A
• Format: Article
• Language: English
• Subjects: Adult; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Dietary Supplements; Endocrinology & Metabolism; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Humans; JNK; Kinases; Nitrates - metabolism; Nitrotyrosine; p38-MAPKα; Placebos; Placenta - metabolism; Pre-eclampsia; Pre-Eclampsia - drug therapy; Pre-Eclampsia - metabolism; Pregnancy; Pregnancy in Diabetics - drug therapy; Pregnancy in Diabetics - metabolism; Pregnancy Proteins - metabolism; Protein Processing, Post-Translational; Proteins; Rodents; Type 1 diabetes mellitus; Tyrosine - metabolism; Vitamin C; Vitamins - pharmacology; Vitamins - therapeutic use
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2013.02.001

Abstract Aim 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. Conclusion 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.