Disease relevance of PZP

• There was no correlation between PZP (or alpha 2M) concentrations and the pTNM-classification or metastatic burden of the breast cancer patients [1].
• Thus, PZP levels in breast cancer patients did not differ from those of fibroadenoma patients or healthy women [1].
• A full-length cDNA clone of the human pregnancy zone protein (PZP) was cloned from the hepatocellular carcinoma cell line Hep3B [2].
• Temperature-dependent biosynthesis of thiol esters in baculovirus recombinant alpha 2M and PZP [3].
• Plasmatic levels of pregnancy zone protein (PZP) increase in children with acute Chagas disease [4].

High impact information on PZP

• In contrast, PZP was localized in blood vessel walls, parenchymal structures within the villous, as well as in the trophoblast cytoplasm [5].
• Frozen sections of human placenta were examined for the presence of four human pregnancy proteins, pregnancy-associated plasma proteins A and C (PAPP-A and PAPP-C), human chorionic somatomammotropin (hCS), and pregnancy zone protein (PZP), by the indirect immunofluorescence technique [5].
• 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 alpha 2M indeed are extensively homologous [6].
• Like A2M and PZP, A2ML1 is located on chromosome 12p13.31 [7].
• 35Cl NMR has been used to follow binding of zinc and manganese to apo-PZP [8].

Biological context of PZP

• Human alpha 2M, PZP and the related pseudogene were mapped to the human chromosome 12p12-13, with the help of gene-specific probes and in situ hybridization [9].
• The proteinase is thus covalently linked to alpha 2M/PZP but its active site is not affected [10].
• With available monoclonal antibodies directed toward alpha 2M and prepared toward PZP, only a limited cross-reaction was observed [11].
• It is concluded that the increase in alpha 1at partly compensates for the fall in AT III, that the rise in PZP presumably enhances fibrinolysis, and that LNg has higher anti-estrogenicity and androgenicity than DSG [12].
• Prospective studies of pregnant women were performed to compare individual variations in the plasma concentration of sex hormone binding globulin (SHBG) and pregnancy zone protein (PZP) during pregnancy, and to elucidate the degree of co-variation between these oestrogen sensitive proteins during gestation [13].

Anatomical context of PZP

• Pregnancy zone protein (PZP) was isolated from late pregnancy serum and examined for binding to normal skin fibroblasts in culture [11].
• Levels of pregnancy zone protein (PZP) were more than doubled at the time of oocyte aspiration compared to the unstimulated cycles [14].
• Chorionic villi prepared from normal full-term placentae were approximately half occupied by endogenous alpha 2M or PZP complexes [15].
• Neither of them were found to exhibit any detectable increase in PZP concentration during culture, but cultures of monocytes were found to produce alpha 2-M [16].
• Based upon these findings, we hypothesize that PZP and PP14 form a stable complex in the plasma of pregnant women and together act synergistically to selectively modulate T-cell activation [17].

Associations of PZP with chemical compounds

• Methylamine reacts with the beta-cysteinyl-gamma-glutamyl thiol ester groups of PZP in a second-order process with k = (13.6 +/- 0.5) M-1 s-1, pH 7.6, 25 degrees C. The reaction product is PZP(dimers); no PZP(tetramers) are formed [18].
• 71% of the corresponding amino acid residues in PZP and human alpha 2-macroglobulin (alpha 2M) are identical and all cysteine residues are conserved [2].
• PZP binds proteinases which cause the cleavage of internal thiol esters in the molecule [19].
• The final preparations of both alpha 2M and PZP are pure as determined by nonreducing and reducing polyacrylamide gel electrophoresis following silver staining and no cross-contamination can be observed [20].
• SHBG capacity and PZP level were measured in 49 women treated with three different combinations of ethinyloestradiol and norethisterone [21].

Physical interactions of PZP

• TGF-beta 2 and TGF-beta 1 bind to PZP in a predominantly noncovalent manner in vitro [22].
• Our studies also indicate that PZP binds TGF-beta 2 with higher affinity than TGF-beta 1 [22].
• The proteinase-binding specificity of PZP is far more restricted than that of alpha 2M [18].
• The PZP C-terminal fragment was demonstrated to bind to the LRP/alpha 2M-receptor [23].

Enzymatic interactions of PZP

• Pregnancy zone protein was cleaved at Thr693-Tyr694 and alpha2-macroglobulin at Gly679-Leu680 and Arg696-Leu697 by matrix metalloproteinase-2 [24].

Regulatory relationships of PZP

• Pregnancy zone protein inhibits production of interleukin-2 but does not affect interleukin-2 receptor expression on T cell activation [25].
• The oestrogenic effects of tamoxifen upon FSH, prolactin and the oestrogen induced Pregnancy Zone Protein (PZP) in postmenopausal women, described in a previous communication from this group, are probably not due to any increase in the serum oestrogens since this increase is transient and hardly impressive [26].

Other interactions of PZP

• The increased level of PZP during pregnancy may affect the action of TGF-beta by regulating the distribution, clearance and/or general availability of TGF-beta [22].
• Normal PZP serum levels are > 100 fold lower than those of alpha 2M [10].
• It is concluded that native PZP molecules are dimers of disulfide-bridged 180-kDa subunits and that proteinase binding results in covalent 1:1 (tetrameric)PZP-enzyme complexes [18].
• Primary structure of pregnancy zone protein. Molecular cloning of a full-length PZP cDNA clone by the polymerase chain reaction [2].
• The resultant serum levels of 17 beta-oestradiol, total oestrone and three liver proteins: sex-hormone-binding globulin (SHBG), pregnancy-zone protein (PZP) and caeruloplasmin were followed [27].

Analytical, diagnostic and therapeutic context of PZP

• NMR and ESR spectroscopies have been used to examine the plasma protease inhibitor pregnancy zone protein (PZP) and its complex with chymotrypsin [8].
• However, better protection of the rectal wall during cryoablation of the peripheral zone of the prostate (PZP) may permit deeper freezing of the PZP and for longer time, rendering the procedure safer and more effective [28].
• The receptor binding domain of PZP can be cleaved from the PZP-methylamine complex by papain and isolated from the other peptides by S-200 gel filtration [20].
• Pure and native PZP, with a recovery of nearly 25% and biological activity of protease-binding, was obtained by two definitive final steps consisting of zinc-chelate and size-filtration chromatographies [29].
• A simple and sensitive enzyme-linked immunosorbent assay (ELISA) measuring specifically the pregnancy zone protein (PZP) was constructed [16].

References