Disease relevance of SERPINB2

• Clinical groups consisting of pregnant women with either severe preeclampsia or chronic hypertension with superimposed severe preeclampsia, as well as normal pregnant and nonpregnant women, were analyzed in a panel of functional and immunologic assays for PAI-1 and PAI-2 [1].
• In contrast, PAI-2 levels were reduced in preeclamptic patients with infarction in comparison with those of patients without infarction (141 ng/mL v 212.9 ng/mL) [1].
• The patients with chronic hypertension and superimposed severe preeclampsia exhibited PAI-2 levels comparable to those of the pure preeclamptic group, whereas their antigenic and functional PAI-1 levels were intermediate (94 ng/mL and 3.25 U/mL, respectively) between the normal pregnant and the pure preeclamptic groups [1].
• However, only PAI-2 reduced the incidence of lung and brain metastasis following liver gene transfer [2].
• Neither PAI-1 nor PAI-2 could be detected in Bowes melanoma cells or in a renal adenocarcinoma cell line (ACHN), while the histiocytic lymphoma cell (U-937) produced only PAI-2 [3].

Psychiatry related information on SERPINB2

• Localization of type 2 plasminogen activator inhibitor (PAI-2) was investigated immunohistochemically in postmortem brain tissue of control subjects and patients with Alzheimer's disease (AD) [4].
• After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function [5].
• In the first study, 226 women were administered the Personality Assessment Inventory, borderline scales (PAI-BOR; L.C. Morey, The Personality Assessment Inventory, Professional Manual, 1991) and a questionnaire that assessed time in menstrual cycle and use of oral contraceptives, that is synthetic estrogens [6].
• RESULTS: Physical activity index (PAI = 24 h EE/SMR) on day 1 (part 1) was 1.55 +/- 0.04, close to the predicted value of 1.5, but between-subject variation was large (range: 1.39-1.68) [7].
• We classified a sample of criminal defendants as high, moderate, or low in psychopathy, based on PCL-R scores, and compared their scores on indices typically used to detect malingering on the MMPI-2, the PAI and the SIRS [8].

High impact information on SERPINB2

• The serine proteinase inhibitor (serpin) plasminogen activator inhibitor type 2 (PAI-2) is well characterized as an inhibitor of extracellular urokinase-type plasminogen activator [9].
• This protection did not appear to be related to an effect on apoptosis but was associated with a PAI-2-mediated induction of constitutive low-level interferon (IFN)-alpha/beta production and IFN-stimulated gene factor 3 (ISGF3) activation, which primed the cells for rapid induction of antiviral genes [9].
• PAI-2 was also induced in macrophages in response to viral RNA suggesting that PAI-2 is a virus response gene [9].
• This primed phenotype was associated with a rapid development of resistance to infection by the PAI-2 transfected cells and the establishment of a persistent productive infection [9].
• These observations, together with the recently demonstrated PAI-2-mediated inhibition of tumor necrosis factor-alpha induced apoptosis, (a) illustrate that PAI-2 has an additional and distinct function as an intracellular regulator of signal transduction pathway(s) and (b) demonstrate a novel activity for a eukaryotic serpin [9].

Chemical compound and disease context of SERPINB2

• Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin [10].
• This inhibition was not due to cellular toxicity, the phospholipidlike nature of lipid X, interference with the PAI-2 assay, or monocyte production of a substance interfering with PAI-2 [11].
• Both PAI and procoagulant factors play an important role in the pathophysiology of inflammation, DIC, and ischemia [12].
• The 214 patients showing significant coronary artery stenosis (greater than 50% reduction of luminal area in any of the great coronary arteries) had higher mean levels of tPA (P less than 0.001) and PAI (P less than 0.01) than a random population sample of similar age [13].
• Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity [14].

Biological context of SERPINB2

• Furthermore, the interaction of ch-uPA(RRHR) with PAI-2 was also substantially enhanced, while the interaction with other members of the serine proteinase inhibitor superfamily, protein nexin 1, alpha1-PI, and C1-inhibitor, was unaffected indicating that the RRHR motif is not a general serine proteinase inhibitor binding site [15].
• During early puerperium of both normal pregnant women and patients, plasma PAI-1 antigen and activity decreased within one day to approximately the levels detected in normal nonpregnant women, while PAI-2 levels remained elevated for over 11 days [1].
• In amniotic fluid, PAI-1 antigen levels increased from 194 +/- 109 ng/ml (first trimester) to 640 +/- 396 ng/ml (third trimester) and PAI-2 antigen levels increased from 72 +/- 57 ng/ml to 173 +/- 97 ng/ml [16].
• The role of PAI-2 in the inhibition of peritoneal fibrinolysis during inflammation was investigated in this study [17].
• The effect of cervical dilatation on PA and PAI concentrations was compared in a laminaria tent group and a mechanical dilatation (control) group [18].

Anatomical context of SERPINB2

• Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological crosstalk in human corneal and conjunctival epithelial cells [19].
• In the present study we have characterized a novel PAI-2-specific ELISA, designed to measure PAI-2 antigen levels in tumor cytosols [20].
• Stimulation of U937 cells with phorbol 12-myristate 13-acetate was accompanied by a further reduction in receptor-bound uPA inhibition by PAI-1 and PAI-2 to 1.7 x 10(6) and 1.1 x 10(5) M-1 s-1, respectively [21].
• In contrast, preincubation of the amnion membrane with PAI-2 which does not bind to the extracellular matrix has no effect on monocyte invasiveness [22].
• However, RA potentiated PMA-mediated induction of PAI-2 mRNA in HL-60 and U937 cells and PAI-2 antigen in all four cell lines [23].

Associations of SERPINB2 with chemical compounds

• We conclude that the PAI-2-specific ELISA described herein is well suited for the measurement of PAI-2 levels in cytosols routinely prepared for analysis of steroid hormone receptors [20].
• Thus, human VSMC produce all three presently known PAI and these can be separated in single heparin affinity purification step [24].
• Synthesis of PAI-1 and PAI-2 is inhibited by actinomycin D and cyclohexamide [25].
• The last decade has seen the generation of several classes of potent and selective Urokinase inhibitor directed to the serine protease domain of the protein which have shown potential anti-cancer effects [26].
• Poly-D-lysine dependent inactivation of tissue plasminogen activator by a class PAI-2 inhibitor (minactivin) [27].

Physical interactions of SERPINB2

• In contrast to the active enzyme, the uPA/PAI-2 complex is rapidly cleared from the monocyte cell surface; this involves an initial cleavage of the complex at the cell surface, followed by endocytosis and degradation [28].
• These data suggest that the predominant form of PAI-2 in placenta extract is heterogeneous and of high molecular mass, containing complexes in which vitronectin is covalently bound to PAI-2 by disulfide bridges [29].
• PAI-2 could bind PRPF8 C-terminal in both the inside and outside of nuclear [30].
• This finding suggested that PAI-2 formed a complex with a target proteinase, which could be involved in mediating the cytolytic activity of TNF [31].

Enzymatic interactions of SERPINB2

• Recombinant human PAI-2 was labeled with [14C]putrescine catalyzed by guinea pig liver transglutaminase [32].
• These data provide evidence for the presence of an endogenous, keratinocyte-derived proteinase that constitutively cleaves intracellular PAI-2 in normal human epidermal keratinocytes [33].

Regulatory relationships of SERPINB2

• Our results indicate that components of the plasminogen activation cascade are up-regulated in endometrial cancer and suggest the role of PAI-2 in determining invasive potential of endometrial carcinomas [34].
• The production of large amounts of PAI-2 may represent an additional control mechanism of proteinase activity [35].
• In contrast, Glu158-scu-PA bound to u-PA receptors on monocytes was only minimally inhibited by a large molar excess of PAI-2 [36].
• In contrast, TNF alpha-induced expression of PAI-2 was synergistically increased by addition of IFN-gamma [37].
• THP-1 cells expressing active PAI-2 also displayed an altered phenotype in response to phorbol ester-induced differentiation that was concomitant with a reduction in CD14 expression [38].

Other interactions of SERPINB2

• This was the result of an increase of PAI-1 antigen; PAI-2 antigen was not detectable [39].
• We speculate that PAI-2 may serve as an inhibitor for uPA in human primary breast cancers [20].
• Here, we show that pRb2/p130 and Rb1/p105, but not p107, interact with PAI-2 in both the cytoplasm and nucleus of normal primary human corneal and conjunctival epithelial cells [19].
• At variance with the former, which was largely released in the culture medium, PAI-2 was mainly cell-associated. t-PA antigen was found in all but two cell lines while u-PA antigen was detected in relatively high concentrations in 8 cell lines [35].
• Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins [25].

Analytical, diagnostic and therapeutic context of SERPINB2

• This report describes the development and use of functional immunoradiometric assays that distinguish the activity of beta-migrating endothelial-type plasminogen activator inhibitor (PAI-1) from that of placental-type plasminogen activator inhibitor (PAI-2) [3].
• In line with this hypothesis, we have studied, by immunohistochemistry, the distribution of PAI-2, uPA and tPA in the normal and in the lesional epidermis of patients with lupus erythematosus (LE), a disease in which epidermal differentiation is disturbed [40].
• Anti-PAI-2 immunofluorescence was found to be strongly concentrated in the amniotic epithelium, but PAI-2 mRNA was negative in this layer, suggesting that the epithelium-associated PAI-2 is not of epithelial origin [41].
• PAI-2 and PAI-1 antigens were measured by enzyme-linked immunosorbent assay, and messenger RNA (mRNA) levels were determined by Northern blot [42].
• Using inducible EJras constructs, we find that increased PAI-2 gene expression is detectable within 6-12 h after treatment with the inducing agent [43].

References