Protein Nitration in Placenta - Functional Significance

R. P. Webster, V. H J Roberts, L. Myatt

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Crucial roles of the placenta are disrupted in early and mid-trimester pregnancy loss, preeclampsia, eclampsia and intrauterine growth restriction. The pathophysiology of these disorders includes a relative hypoxia of the placenta, ischemia/reperfusion injury, an inflammatory response and oxidative stress. Reactive oxygen species including nitric oxide (NO), carbon monoxide and superoxide have been shown to participate in trophoblast invasion, regulation of placental vascular reactivity and other events. Superoxide, which regulates expression of redox sensitive genes, has been implicated in up-regulation of transcription factors, antioxidant production, angiogenesis, proliferation and matrix remodeling. When superoxide and nitric oxide are present in abundance, their interaction yields peroxynitrite a potent pro-oxidant, but also alters levels of nitric oxide, which in turn affect physiological functions. The peroxynitrite anion is extremely unstable thus evidence of its formation in vivo has been indirect via the occurrence of nitrated moieties including nitrated lipids and nitrotyrosine residues in proteins. Formation of 3-nitrotyrosine (protein nitration) is a "molecular fingerprint" of peroxynitrite formation. Protein nitration has been widely reported in a number of pathological states associated with inflammation but is reported to occur in normal physiology and is thought of as a prevalent, functionally relevant post-translational modification of proteins. Nitration of proteins can give either no effect, a gain or a loss of function. Nitration of a range of placental proteins is found in normal pregnancy but increased in pathologic pregnancies. Evidence is presented for nitration of placental signal transduction enzymes and transporters. The targets and extent of nitration of enzymes, receptors, transporters and structural proteins may markedly influence placental cellular function in both physiologic and pathologic settings.

Original languageEnglish (US)
Pages (from-to)985-994
Number of pages10
JournalPlacenta
Volume29
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

Fingerprint

Placenta
Peroxynitrous Acid
Superoxides
Nitric Oxide
Proteins
Reactive Oxygen Species
Pregnancy Trimesters
Pregnancy Proteins
Pregnancy
Eclampsia
Trophoblasts
Dermatoglyphics
Enzymes
Carbon Monoxide
Post Translational Protein Processing
Pre-Eclampsia
Reperfusion Injury
Oxidation-Reduction
Anions
Blood Vessels

Keywords

  • Nitric oxide
  • Oxidative stress
  • Peroxynitrite
  • Placenta
  • Superoxide

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

Webster, R. P., Roberts, V. H. J., & Myatt, L. (2008). Protein Nitration in Placenta - Functional Significance. Placenta, 29(12), 985-994. https://doi.org/10.1016/j.placenta.2008.09.003

Protein Nitration in Placenta - Functional Significance. / Webster, R. P.; Roberts, V. H J; Myatt, L.

In: Placenta, Vol. 29, No. 12, 12.2008, p. 985-994.

Research output: Contribution to journalArticle

Webster, RP, Roberts, VHJ & Myatt, L 2008, 'Protein Nitration in Placenta - Functional Significance', Placenta, vol. 29, no. 12, pp. 985-994. https://doi.org/10.1016/j.placenta.2008.09.003
Webster, R. P. ; Roberts, V. H J ; Myatt, L. / Protein Nitration in Placenta - Functional Significance. In: Placenta. 2008 ; Vol. 29, No. 12. pp. 985-994.
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