Nitrative stress and poly(ADP-ribose) polymerase activation in healthy and gestational diabetic pregnancies

E. M. Horváth, R. Magenheim, E. Kugler, G. Vácz, A. Szigethy, F. Lévárdi, M. Kollai, Csaba Szabo, Z. Lacza

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Aims/hypothesis: Increased oxidative-nitrosative stress, poly(ADP-ribose) polymerase (PARP) activation and subsequent cellular damage play important roles in the complications of both diabetes mellitus and pregnancy. Our aim was to investigate nitrative stress and PARP activity levels during normal and gestational diabetic (GDM) pregnancy in both maternal and fetal tissues. Methods: Blood samples were collected during pregnancy (weeks 16-29 and 36-40), and placental and umbilical cord tissues were harvested after delivery from healthy volunteers and GDM patients subjected to a carbohydrate-restricted diet or insulin treatment. Immunohistochemical staining was performed on leucocytes and tissue sections using anti-nitrotyrosine (NT), anti-poly(ADP-ribose) (PAR) and anti-apoptosis inducing factor antibodies. Results: In healthy pregnancies the intensity of NT and PAR staining of leucocytes correlated positively with gestational week (R 2∈=∈0.43, p∈<∈0.01 and R 2∈=∈0.49, p∈<∈0.001, respectively). In patients on a carbohydrate-restricted diet PAR staining was already strong in weeks 16-29 (p∈<∈0.001 vs control) and did not increase further. In weeks 16-29 there was a correlation between PAR staining and the 2 h value of the oral glucose tolerance test (R 2∈=∈0.49, p∈<∈0.001). Patients with the highest level of leucocyte PARP activity later required insulin therapy, which decreased the intensity of NT and PAR staining. Placental and umbilical cord tissues also had a higher level of nitrative stress markers in GDM pregnancies, but the highest level of PARP activity was observed after insulin therapy. Conclusions/interpretation: Continuous elevation of tyrosine nitration and PARP activation may be considered physiological during pregnancy. However, the high level of PARP activity in early pregnancy may signal the subsequent development of severe GDM.

Original languageEnglish (US)
Pages (from-to)1935-1943
Number of pages9
JournalDiabetologia
Volume52
Issue number9
DOIs
StatePublished - Sep 2009

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Poly(ADP-ribose) Polymerases
Poly Adenosine Diphosphate Ribose
Pregnancy
Staining and Labeling
Carbohydrate-Restricted Diet
Leukocytes
Umbilical Cord
Insulin
Apoptosis Inducing Factor
Pregnancy in Diabetics
Diabetes Complications
Glucose Tolerance Test
Tyrosine
Healthy Volunteers
Oxidative Stress
Fetus
Therapeutics
Mothers
Antibodies
3-nitrotyrosine

Keywords

  • Circulating leucocytes
  • Gestational diabetes
  • Insulin treatment
  • Peroxynitrite
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Horváth, E. M., Magenheim, R., Kugler, E., Vácz, G., Szigethy, A., Lévárdi, F., ... Lacza, Z. (2009). Nitrative stress and poly(ADP-ribose) polymerase activation in healthy and gestational diabetic pregnancies. Diabetologia, 52(9), 1935-1943. https://doi.org/10.1007/s00125-009-1435-3

Nitrative stress and poly(ADP-ribose) polymerase activation in healthy and gestational diabetic pregnancies. / Horváth, E. M.; Magenheim, R.; Kugler, E.; Vácz, G.; Szigethy, A.; Lévárdi, F.; Kollai, M.; Szabo, Csaba; Lacza, Z.

In: Diabetologia, Vol. 52, No. 9, 09.2009, p. 1935-1943.

Research output: Contribution to journalArticle

Horváth, EM, Magenheim, R, Kugler, E, Vácz, G, Szigethy, A, Lévárdi, F, Kollai, M, Szabo, C & Lacza, Z 2009, 'Nitrative stress and poly(ADP-ribose) polymerase activation in healthy and gestational diabetic pregnancies', Diabetologia, vol. 52, no. 9, pp. 1935-1943. https://doi.org/10.1007/s00125-009-1435-3
Horváth, E. M. ; Magenheim, R. ; Kugler, E. ; Vácz, G. ; Szigethy, A. ; Lévárdi, F. ; Kollai, M. ; Szabo, Csaba ; Lacza, Z. / Nitrative stress and poly(ADP-ribose) polymerase activation in healthy and gestational diabetic pregnancies. In: Diabetologia. 2009 ; Vol. 52, No. 9. pp. 1935-1943.
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AU - Vácz, G.

AU - Szigethy, A.

AU - Lévárdi, F.

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