Placental Localization of Human Pregnancy—Associated Plasma Proteins

Lin, Tsue-Ming; Halbert, Seymour P.

doi:10.1126/science.60782

Cited by 149 publications

(42 citation statements)

References 21 publications

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“…The PAPP-A (the IGBP-4 protease) gene maps to the long arm of chromosome 9 and has been well characterized [12]. The PAPP-A gene has an encrypted gene encoding for the proMBP protein which binds to PAPP-A to inhibit its proteolytic effect on IGFBP-4 [2,3].…”

Section: Discussionmentioning

confidence: 99%

“…The PAPP-A gene has an encrypted gene encoding for the proMBP protein which binds to PAPP-A to inhibit its proteolytic effect on IGFBP-4 [2,3]. PAPP-A mRNA is expressed in syncytiotrophoblasts, extravillous cytotrophoblasts, and the extracellular matrix in placental septae [12,13]. PAPP-A protein has a proteolytic domain (PD), three lin-notch repeats domain (LNR), and five complement control protein modules domain (CCP).…”

Section: Discussionmentioning

confidence: 99%

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Low Pregnancy-Associated Plasma Protein-A at 10+1 to 14+6 Weeks of Gestation and a Possible Mechanism Leading to Miscarriage

et al. 2004

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Objective: To compare pregnancy-associated plasma protein-A (PAPP-A) serum levels at 10⁺¹ to 14⁺⁶ weeks gestation in groups of patients with different obstetrical outcomes. Patients and Methods: The medical records of women who had consented to donate blood for biochemical research purposes while their pregnancies were uncomplicated were reviewed to define the clinical groups. After the clinical groups were defined, the donated maternal serum samples were thawed and PAPP-A measured by ELISA. ANOVA was used to compare mean values within groups. Result: All groups had similar gestational ages at blood donation (overall mean 12.5 weeks; no difference in gestational age was found within groups, p = 0.18). The overall PAPP-A serum level was 2.01 mIU/ml with only the spontaneous abortion group having a statistical different PAPP-A level (0.09 mIU/ml; p < 0.001). Conclusion: These data suggest that those women who experienced spontaneous abortions had significantly different mean PAPP-A serum levels at 10⁺¹ to 14⁺⁶ weeks gestation. Several lines of evidence suggest that downregulation of insulin-like growth factor-II availability due to a decreased PAPP-A serum level may be the cause of spontaneous abortion in these women.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Low Pregnancy-Associated Plasma Protein-A at 10+1 to 14+6 Weeks of Gestation and a Possible Mechanism Leading to Miscarriage

et al. 2004

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“…For both rat aMs, the liver is probably the major site of synthesis (60)(61)(62) as it is for a2M (unpublished data). Although PZP has been localized in the villous parenchymal tissue of the placenta and in trophoblasts (63), this organ is probably not the site of its synthesis (64). Though in vitro estrogendependent synthesis of PZP has been demonstrated in cultures of human leukocytes (65)(66)(67), synthesis of PZP by the liver hepatocytes is probably quantitatively most important (68,69).…”

Section: W~h Aveekp Hte T Vr Kyf P Et W I Wnolavavvn S Asgvade Vasavtmentioning

confidence: 99%

Partial primary structure of human pregnancy zone protein: extensive sequence homology with human alpha 2-macroglobulin.

Sottrup‐Jensen¹,

Folkersen²,

Kristensen³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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Human pregnancy zone protein (PZP) is a major pregnancy-associated protein. Its quaternary structure (two covalently bound 180-kDa subunits, which are further non-covalently assembled into a tetramer of 720 kDa) is similar to that of human a2-macroglobulin (a2M). Here we show, from the results of complete or partial sequence determination of a random selection of 38 tryptic peptides covering 685 residues of the subunit of PZP, that PZP and a2M indeed are extensively homologous. In the stretches of PZP sequenced so far, the degree of identically placed residues in the two proteins is 68%, indicating a close evolutionary relationship between PZP and a2M. Although the function of PZP in pregnancy is largely unknown, its close structural relationship to a2M suggests analogous proteinase binding properties and a potential for being taken up in cells by receptor-mediated endocytosis. In this regard our studies indicate a bait region in PZP significantly different from that present in a2M. PZP could be the human equivalent of the acute-phase a-macroglobulins (e.g., rat a2M and rabbit a1M) described earlier.Human "pregnancy zone protein" (PZP) § is one of the major pregnancy-associated plasma proteins. PZP was first described in 1959 by Smithies (2) who, upon zone-electrophoresis in starch gels, detected a characteristic band from the sera of some pregnant women. Subsequent work showed that PZP was a prominent constituent of late-pregnancy sera (3,4). In healthy non-pregnant females and in males, PZP is present in trace amounts only (females: 10-30 mg/liter of plasma; males: <10 mg/liter of plasma) (5). During pregnancy, the plasma concentration of PZP increases and may reach levels of 1000-1400 mg/liter just before term (5-7). Small amounts of PZP have been prepared from pregnancy serum and plasma or from placental extracts by elaborate conventional procedures or more recently by immunoadsorbent techniques (8)(9)(10)(11)(12)(13)(14)(15)(16). PZP is a glycoprotein of a2-mobility (2-4, 8, 9) containing 10-12% carbohydrate (11-13). Preparations of PZP when subjected to denaturation under non-reducing conditions display a 360-kDa molecular species (12,13,16) Proteins structurally and functionally related to human a2M have been found in the plasma of members of all major vertebrate taxa (19). Two distinct a-macroglobulins (aMs) having slightly different electrophoretic mobility have been described in the rat (a1M and a2M) (20-22), the rabbit (a1M and a2M) (23, 24), the dog (a1M and a2M) (25), and the pig ("slow" aM and "fast" aM) (26). Of the two aMs found in the rat and the rabbit, rat a2M and rabbit a1M are acutephase reactants, since their plasma levels are greatly increased during experimental inflammation and under a variety of stress conditions. In contrast, the plasma levels of rat a1M and rabbit a2M, like human a2M, are only slightly affected under these conditions (20)(21)(22)(23)(27)(28)(29)(30)(31)(32). The observation that the plasma concentration of rat a2M is increased during pregnancy (28-30) indic...

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“…They all decreased sharply after childbirth, with half lives of less than 1 day for HCS and PAPP-B, 1-2 days for PAPP-C and 3-4 days for PAPP-A. The available data indicate that they are all products of the placental trophoblast [7,9,[19][20][21]. Analogous PAPPs were also re vealed in the pregnant rat and mouse by similar immunological methods [22].…”

Section: Introductionmentioning

confidence: 99%

“…In a series of reports since 1972 [1][2][3][4][5][6][7][8][9], our laboratory has described four distinct human pregnancy-associated plasma prote 1 These investigations were supported by a re search grant from the National Institutes of Health (HD-05736).…”

Section: Introductionmentioning

confidence: 99%

Immunological Relationships of Human and Subhuman Primate Pregnancy-Associated Plasma Proteins

Lin¹,

Halbert²

1978

Int Arch Allergy Immunol

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(1) Four pregnancy-associated plasma proteins cross-reactive with antibodies to the human pregnancy proteins were detected in several species of pregnant subhuman primates. In the case of the two apes studied (chimpanzee and orangutan), these appeared to be immunologically identical to the human PAPPs (PAPP-A, -B, -C, and HCS). In the old world monkeys analyzed, equivalent partially cross-reactive PAPPs were found; while in the new world squirrel monkey, only faint traces of cross-reactive PAPP-C and HCS were observed with the most sensitive methods used. (2) As in the human, these proteins appeared to be specific for pregnancy, not being detectable in nonpregnant animals, female or male. (3) The pregnant chimpanzee possessed significantly higher concentrations of PAPP-A and PAPP-C than did women at an equivalent stage of pregnancy, while the HCS and PAPP-B levels appeared to be approximately the same. (4) The primate PAPP-C analogues were more complex than human PAPP-C, often revealing multiple gel diffusion patterns with subfractions of differing electrophoretic mobilities. (5) Based on the changes of electrophoretic mobility upon exposure to neuraminidase, the subhuman primate as well as human PAPP-A and PAPP-C appeared to be glycoproteins containing sialic acid. (6) In the chimpanzee and rhesus monkey, as in the human, the levels of PAPP-A, PAPP-C, and HCS were appreciably higher during the third trimester of pregnancy than they were during the second trimester.

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Placental Localization of Human Pregnancy—Associated Plasma Proteins

Cited by 149 publications

References 21 publications

Low Pregnancy-Associated Plasma Protein-A at 10<sup>+1</sup> to 14<sup>+6</sup> Weeks of Gestation and a Possible Mechanism Leading to Miscarriage

Low Pregnancy-Associated Plasma Protein-A at 10<sup>+1</sup> to 14<sup>+6</sup> Weeks of Gestation and a Possible Mechanism Leading to Miscarriage

Partial primary structure of human pregnancy zone protein: extensive sequence homology with human alpha 2-macroglobulin.

Immunological Relationships of Human and Subhuman Primate Pregnancy-Associated Plasma Proteins

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