Formation of high-molecular-weight angiotensinogen during pregnancy is a result of competing redox reactions with the proform of eosinophil major basic protein

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  • Søren Kløverpris, Danmark
  • Louise Lind Skov, Danmark
  • Simon Glerup
  • Kasper Pihl, Statens Serum Institut, Danmark
  • Michael Christiansen, Statens Serum Institut, Danmark
  • Claus Oxvig
The plasma concentration of the placentally derived proMBP (proform of eosinophil major basic protein) increases in pregnancy, and three different complexes containing proMBP have been isolated from pregnancy plasma and serum: a 2:2 complex with the metalloproteinase, PAPP-A (pregnancy-associated plasma protein-A), a 2:2 complex with AGT (angiotensinogen) and a 2:2:2 complex with AGT and complement C3dg. In the present study we show that during human pregnancy, all of the circulating proMBP exists in covalent complexes, bound to either PAPP-A or AGT. We also show that the proMBP-AGT complex constitutes the major fraction of circulating HMW (high-molecular weight) AGT in late pregnancy, and that this complex is able to further associate with complement C3 derivatives post-sampling. Clearance experiments in mice suggest that complement C3-based complexes are removed faster from the circulation compared to monomeric AGT and the proMBP-AGT complex. Furthermore, we have used recombinant proteins to analyse the formation of the proMBP-PAPP-A and the proMBP-AGT complexes, and we demonstrate that they are competing reactions, depending on the same cysteine residue of proMBP, but differentially on the redox potential, potentially important for the relative amounts of the complexes in vivo. These findings may be important physiologically, since the biochemical properties of the proteins change as a consequence of complex formation.
OriginalsprogEngelsk
TidsskriftBiochemical Journal
Vol/bind449
Nummer1
Sider (fra-til)209-217
Antal sider9
ISSN0264-6021
DOI
StatusUdgivet - 1 jan. 2013

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