Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein

Oxvig, Claus; Sand, Ole; Kristensen, Torsten Nygaard; Gleich, Gerald J.; Sottrup‐Jensen, Lars

doi:10.1016/s0021-9258(18)31378-4

Cited by 161 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Contamination with SP1 antigen might well have been present; this protein is structurally unrelated to PAPP-A but very abundant, leading to the presence of anti-SP1 antibodies in polyclonal anti-PAPP-A antisera (Bersinger et al, 1995b;Bersinger, 1996). On the other hand, there may be a biological link between PAPP-A and haptoglobin (Bueler and Bersinger, 1989) and certainly for pro-MBP for which such an association has been demonstrated (Oxvig et al, 1993). The polyclonal antibody preparations tested here all recognize the pro-MBP epitopes and, as a consequence, are cross-reacting with PAPP-A, the complement C3 subunit, and angiotensinogen.…”

Section: Discussionmentioning

confidence: 72%

“…PAPP-A-2 was obtained by direct immunoadsorption of a pool of late pregnancy serum on an affinity column prepared by binding one anti-PAPP-A monoclonal antibody (APS18, see below) to CNBr-activated Sepharose (Pharmacia). After elution, this preparation was reduced and carboxymethylated as described (Oxvig et al, 1994) and then put through a Superose-6 chromatographic column (Pharmacia) to separate PAPP-A from the proform of eosinophil major basic protein (pro-MBP) to which it is associated (Oxvig et al, 1993).…”

Section: Purification and Characterization Of Papp-a Antigen Isolation Of Papp-amentioning

confidence: 99%

See 1 more Smart Citation

Production and characterization of monoclonal antibodies against pregnancy-associated plasma protein A

Bersinger

Meisser²,

Bessou³

et al. 1999

Molecular Human Reproduction

View full text Add to dashboard Cite

Pregnancy-associated plasma protein A (PAPP-A) was found to be a good first trimester maternal serum marker, together with free beta-human chorionic gonadotrophin (HCG) subunits, for the biochemical screening of fetal trisomy 21 (Down's syndrome). We have raised monoclonal antibodies (mAbs) against PAPP-A purified from human pregnancy serum. The different antibodies were characterized biochemically by Western blot analysis and in terms of specificity (reaction with non-pregnant and male serum). Their performance in Down's syndrome screening was assessed in comparison with an existing enzyme-linked immunosorbent assay method after labelling of the different mAbs with biotin or horseradish peroxidase. A pair of mAbs was eventually chosen for a double-antibody sandwich protocol. The selected combination was found to have a significantly increased specificity (P = 0.0116) over the method using (purified) polyclonal antibodies, together with slightly increased sensitivity. In our limited number of Down's syndrome pregnancy samples (n = 17) and controls (n = 18), the medians as well as the multiples of the median values (for the affected cases) were comparable between the two methods described.

show abstract

Section: Discussionmentioning

confidence: 72%

Section: Purification and Characterization Of Papp-a Antigen Isolation Of Papp-amentioning

confidence: 99%

Production and characterization of monoclonal antibodies against pregnancy-associated plasma protein A

Bersinger

Meisser²,

Bessou³

et al. 1999

Molecular Human Reproduction

View full text Add to dashboard Cite

show abstract

“…1,16 Plazmatický protein A spojený s těhotenstvím je v těhotenském séru disulfi dickými můstky (2 : 2) vázán s proformou hlavního bazického proteinu eosinofi lů (proMBP) (~ 500 kDa). 17 Proforma hlavního bazického proteinu eosinofi lů slouží jako fyziologický inhibitor PAPP-A a za měřitelnou aktivitu PAPP-A pravděpodobně odpovídá menší sub populace jen částečně inhibovaného PAPP-A v komplexu s proMBP v poměru 2 : 1. 18 Qin a spol.…”

Section: Podpořeno Grantem Mzofnm2005unclassified

Pregnancy-associated plasma protein-A in the pathophysiology, diagnosis, and prognosis of coronary heart disease

Hájek¹,

Maçek²

2010

Cor Vasa

View full text Add to dashboard Cite

Plazmatický protein A spojený s těhotenstvím (PAPP-A) je potenciálním markerem vulnerabilního plátu. Vzhledem ke známým patofyziologickým vlastnostem má teoretické předpoklady k užití nejen v časné diagnostice akutního koronárního syndromu a jeho prognózy, ale i ve stratifi kaci rizika pacientů bez klinických známek koronární nemoci. O tom, zda se stanovení PAPP-A stane součástí klinické praxe, či zda upadne v zapomnění jako řada jiných, zpočátku nadějných markerů, rozhodne skutečnost, jestli se podaří vyřešit otázky jeho rychlého, přesného a široce dostupného stanovení. Avšak, i když se nakonec v rutinní diagnostice akutního koronárního syndromu užívat nebude, je pravděpodobné, že další studium patofyziologie PAPP-A a IGF přinese řadu významných poznatků o vzniku a rozvoji jak aterosklerotického postižení, tak i obecných dějů buněčného stárnutí. Klíčová slova: Plazmatický protein A spojený s těhotenstvím -Ischemická choroba srdeční Hájek P. Pregnancy-associated plasma protein-A in the pathophysiology, diagnosis, and prognosis of coronary heart disease.

show abstract

“…First, the majority of IGF-1 is bound by one of six IGF-binding proteins (IGFBPs), which typically sequester IGF-1 and prevent receptor activation (34). Second, IGFBP proteinases can liberate IGF-1 by proteolytic cleavage of IGFBPs (64), and third, IGFBP proteinases are regulated by proteinase inhibitors (52,60,80,81). IGFBP-bound IGF-1 can therefore be considered a reservoir of IGF-1 that can be liberated in a spatiotemporal manner by IGFBP proteolysis depending on the presence and activity of various proteinases in different tissues (82) (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Little is known about the regulation of PAPP-A gene expression, but three endogenous PAPP-A inhibitors have been identified: The proform of eosinophil major basic protein, which inactivates the vast majority of circulating placentaderived PAPP-A in pregnancy (80,81), and stanniocalcin-1 and -2 (STC1 and -2), which appear to regulate PAPP-A within different tissues, including arteries (51,52,60,112). STC1 inhibits by high-affinity (pM) binding to PAPP-A or PAPP-A2, stimulates hepatic IGF-1 secretion into the circulation (2).…”

Section: Introductionmentioning

confidence: 99%

PAPP-A and the IGF system in atherosclerosis: what’s up, what’s down?

Steffensen

Conover

Oxvig

2019

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) from IGF-binding protein-2, -4, and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF-1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF-1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what’s up and what’s down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.

show abstract

Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein

Cited by 161 publications

References 0 publications

Production and characterization of monoclonal antibodies against pregnancy-associated plasma protein A

Production and characterization of monoclonal antibodies against pregnancy-associated plasma protein A

Pregnancy-associated plasma protein-A in the pathophysiology, diagnosis, and prognosis of coronary heart disease

PAPP-A and the IGF system in atherosclerosis: what’s up, what’s down?

Contact Info

Product

Resources

About