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Results for “ALPHA GLOBULIN”

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At least 19 recordsLinked to original sources
PubMed2002

The interaction of human and bovine serum proteins with CYP3A in human liver microsomes: inhibition of testosterone 6beta-hydroxylation by albumin, alpha-globulins, alpha(1)-acid glycoprotein and gamma-globulins.

The effects of human and bovine serum proteins on CYP3A activity, using testosterone as the probe substrate, were investigated in human liver microsomes. Serum albumin, alpha-globulins, and alpha(1)-acid glycoprotein (alpha(1)-AGP) of both species significantly inhibited testosterone 6beta-hydroxylation. When the inhibitory effects of serum proteins were compared with serum protein binding data, human alpha-globulins, with a ratio (relative metabolic activity/unbound fraction) of 0.3, showed higher, and bovine alpha(1)-AGP, with the ratio of 1.4, showed lower inhibitory effects than those expected from protein binding of testosterone. The effects of the other serum proteins were close to those expected from protein binding, according to the free drug hypothesis. The K(i) values obtained from the Dixon plots were 0.32% (w/v, 48 microM) for human serum albumin (HSA), 0.48% for human alpha-globulins, and 0.23% (52 microM) for human alpha(1)-AGP. K(i) values of bovine serum albumin, bovine alpha-globulins and bovine alpha(1)-AGP were 3-5 times higher than those of the respective human proteins. The results suggest a direct interaction of some of these serum proteins with the active site of the CYP3A isoform. Since the bovine serum proteins showed weaker inhibitory effects than human serum proteins, the wide use of BSA, which is viewed as interchangeable with HSA, needs to be cautioned.

Alpha-Globulins↗
PubMed2003

Interaction of serum proteins with CYP isoforms in human liver microsomes: inhibitory effects of human and bovine albumin, alpha-globulins, alpha-1-acid glycoproteins and gamma-globulins on CYP2C19 and CYP2D6.

The effects of serum proteins on the in vitro hydroxylation pathways of mephenytoin (CYP2C19) and debrisoquine (CYP2D6) were studied to enhance the predictability of in vivo drug metabolism from in vitro assays. Both CYP substrates are known to be weakly bound to albumin and the applicability of the free drug hypothesis was further appraised. Since bovine serum albumin (BSA) is used widely in in vitro assays, a comparison between human and bovine proteins was made. Four major serum proteins were studied: albumin, alpha1-acid glycoprotein (AGP), alpha- and gamma-globulins. Human serum albumin (HSA) inhibited both CYP activities about 20% more than BSA. The addition of human alpha-globulins, but not the bovine protein, resulted in marked reduction of 86% and 41% in CYP2C19 and CYP2D6 activities, respectively. This reduction of activity was strikingly greater than the fraction bound (14 and 22%, respectively). The inhibition was of the competitive type and the Ki values of human alpha-globulins on CYP2C19 and CYP2D6 were found to be 0.45% (4.5 mg/ml) and 3.5% (35 mg/ml), respectively. The effect of both human and bovine gamma-globulins on CYP isoforms was negligible. The Ki values of human and bovine AGP for CYP2C19 were 1.84% (420 microM) and 0.93% (210 microM), respectively. For HSA, human alpha-globulins and human and bovine AGP, the strongly decreased CYP activities in vitro cannot be explained by the free drug hypothesis. A direct interaction of these serum proteins with CYP enzymes is postulated. Differential effects of bovine and human serum proteins and CYP specific inhibition were observed.

Alpha-Globulins↗
PubMed1971

Isolation and characterization of human foetal alpha-globulin (alpha 1F) from foetal and hepatoma sera.

The alpha 1F present in human foetal sera and the serum from a patient with hepatocellular carcinoma was isolated by immune precipitation using rabbit anti-alpha 1F. After labelling with 125I, some physicochemical properties of alpha 1F were investigated. The molecular weights of 125I-labelled alpha 1F isolated from foetal and hepatoma sera were 61,000 and 63,000, respectively. The protein was not dissociated in 6 M guanidine after complete reduction, showing that it contains a single peptide chain.

Alpha-Globulins↗
PubMedDate not supplied

Immunochemical and biochemical relationship between human pregnancy-associated secreted endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG) and the soluble placental proteins 12 and 14 (PP12 and PP14).

Two proteins, pregnancy-associated endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG), synthesized de novo and secreted by the human endometrium and decidua during pregnancy, have been demonstrated to be immunochemically related to the soluble placental proteins PP12 and PP14 isolated from term placenta. However, although these immunochemically similar endometrially- and placentally-derived proteins differ in their reported biochemical properties, in this report we have demonstrated that PP12 and PP14 are biochemically identical to alpha 1- and alpha 2-PEG with respect to subunit size. We conclude that these placental proteins are derived from the endometrium by de novo synthesis, and we suggest that the localization of these proteins to the placenta reflects either absorption, specific binding or processing by the trophoblast. The significance of clinical studies involving PP12 and PP14 measurement must therefore be reassessed in the light of their exclusive endometrial origin.

Abortion, Therapeutic↗
PubMed1986

Purification of human secretory pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) from cytosol of first trimester pregnancy endometrium.

Pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein as assessed by in-vitro synthesis and secretion by the endometrium during the luteal phase of the menstrual cycle and early first trimester of pregnancy, has been purified from the cytosolic fraction of pregnancy endometrium. The purification schedule involved anion exchange chromatography (DE52), gel filtration (Sephacryl S-200), concanavalin A-Sepharose, chromatofocusing and negative immunoaffinity chromatography. On anion exchange chromatography alpha 2-PEG eluted at 0.11 M NaCl, on Sephacryl S-200 with an apparent Mr of 56 K, it bound to concanavalin A and eluted from a chromatofocusing column at a pH of 4.6. alpha 2-PEG was isolated with 98% purity, as assessed by one-dimensional sodium dodecyl sulphate (SDS)-gradient polyacrylamide gel electrophoresis (subunit Mr under reducing conditions 28 K), and a yield of 0.11 mg per g wet weight tissue. This purified alpha 2-PEG should enable in-vitro assessment of the function of this unique protein in implantation and pregnancy and provide antigenic material for the development of a radioimmunoassay.

Chromatography, Affinity↗
PubMed1987

Development and validation of a radioimmunoassay for human secretory 'pregnancy-associated endometrial alpha 2-globulin' (alpha 2-PEG) and detection in serum during pregnancy.

A specific and sensitive radioimmunoassay has been developed for pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the human endometrium during the mid- to late-luteal phase of the menstrual cycle and first trimester of pregnancy. This assay enabled alpha 2-PEG to be measured in the cytosolic extracts of endometrium, amniotic fluid, seminal plasma and in pregnancy sera. The concentration of alpha 2-PEG in cytosols prepared from mid-secretory endometrium was 44-fold higher than in those from proliferative endometrium and a further 30-fold increase during the first trimester in comparison with mid-secretory endometrium. Levels of alpha 2-PEG in amniotic fluid (15-20 weeks) and seminal plasma were 15 +/- 4 and 55 +/- 7 micrograms/ml, respectively. With the exception of sera, where alpha 2-PEG was undetectable using rocket immunoelectrophoresis, estimates of alpha 2-PEG levels in these compartments, measured by rocket immunoelectrophoretic and RIA assays were comparable, although for seminal plasma 2.5-fold higher estimates were obtained by RIA. Detectable levels of alpha 2-PEG were obtained in 253 of 275 (92%) pregnancy sera tested. During pregnancy, peak levels were detected between weeks 6 and 11 but these represented only 2% of the levels detected in amniotic fluid. These observations support evidence from in vitro studies that alpha 2-PEG is a product of the secretory glandular epithelium, a tissue prominent in the first trimester and whose principal secretory route during pregnancy is into the amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗
PubMed1989

Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) during normal menstrual and combined oral contraceptive cycles and relationship to immunohistological localization.

Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the endometrium during the late luteal phase of the menstrual cycle and early pregnancy, were measured serially during normal menstrual cycles and in women taking various combined oral contraceptives. Pill users were also sampled on an individual basis. Endometrium from women taking the combined oral contraceptive was examined immunohistochemically using a monoclonal antibody to alpha 2-PEG. Levels of alpha 2-PEG in the menstrual cycle sera showed consistent changes following the luteinizing hormone peak, with a greater than three-fold increase between basal levels at mid-cycle and those in the late luteal phase. Serum levels of alpha 2-PEG in the pill users remained at basal levels throughout the cycle, regardless of the progestagen in the formulation. This finding was noted in serial and individual samples from both monophasic and triphasic preparations. However, there was evidence of induction of alpha 2-PEG production at the local endometrial level when immunohistochemical staining was employed at various stages of the pill cycle. This suggests that serum levels of alpha 2-PEG may not necessarily reflect local endometrial production of the protein. These observations are discussed with reference to the proposed value of serum measurement of this protein in assessing relative progestagenic activity upon the endometrium.

Adult↗
PubMed1990

Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated beta-lactoglobulin homologue, in successful and unsuccessful assisted conception.

Pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) is the major secretory protein of the endometrium in the late luteal phase. Serum levels were measured during the implantation period in successful and unsuccessful cycles of assisted conception. The effects of two different treatment regimens were also compared. All patients who underwent ovulation induction therapy showed an endometrial response as measured by a rise in serum levels of alpha 2-PEG. This rise was the same regardless of either implantation or the method of ovulation induction used. Higher levels were seen at oocyte recovery in those cycles treated with clomiphene citrate and may reflect a disordered endometrial response involving a direct effect of the drug on the endometrium. This may explain the difference in success rates in assisted conception when an alternative treatment initially involving down-regulation of endogenous gonadotrophin activity and subsequent administration of gonadotrophins is used. The rise in serum levels seen in pregnancy did not differ statistically according to whether the pregnancy progressed normally or subsequently aborted. Considerably reduced alpha 2-PEG production by the endometrium was identified in one patient who subsequently aborted. The measurement of serum levels of alpha 2-PEG during the implantation phase is unlikely to provide a clinical tool either for early detection of pregnancy or as a prognostic factor of successful implantation.

Abortion, Spontaneous↗
PubMed1986

Amniotic fluid concentrations of secreted pregnancy-associated endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG).

The levels of pregnancy-associated endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG), the two major proteins synthesized and secreted by the endometrium in vitro, have been assayed in 210 amniotic fluid specimens obtained at termination of pregnancy or by amniocentesis, or at delivery. alpha 1-PEG was undetectable until week 10 and thereafter rose to peak levels between weeks 20 and 24. Levels fell 15-fold by week 35 but substantial amounts were still present at parturition. alpha 2-PEG was present at highest levels during early pregnancy, at weeks 6-15, but thereafter levels rapidly fell until during weeks 31-42 alpha 2-PEG was detectable in only 3 of 25 specimens. During weeks 15-20, when alpha 2-PEG levels fell and alpha 1-PEG levels rose, a high correlation was observed between the week of gestation and the log of the ratios of the concentration of these proteins. These observations provide the opportunity to assess the role of endometrial and decidual dysfunction in the aetiology of pregnancy disorders.

Amniotic Fluid↗
PubMed1988

Immunohistological localization of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) in endometrial adenocarcinoma and effect of medroxyprogesterone acetate.

Endometrium from postmenopausal women with endometrial adenocarcinoma was examined immunohistochemically using a monoclonal antibody to pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the glandular epithelium during the late luteal phase of the menstrual cycle and early pregnancy. Specimens were obtained at initial diagnostic curettage and at hysterectomy after medroxyprogesterone acetate (MPA) therapy. alpha 2-PEG was not detected in any malignant tissue irrespective of histological differentiation. Non-malignant endometrium obtained in association with malignant tissue was negative for alpha 2-PEG before treatment although after MPA therapy all specimens obtained exhibited marked alpha 2-PEG localization in glands. In four specimens endogenous alkaline phosphatase was observed consistently only in the malignant endometrium. Malignant endometrium does not appear to synthesize alpha 2-PEG nor is its synthesis induced by an oral progestogen, so that it does not represent a useful marker for endometrial carcinoma. Non-malignant endometrium in postmenopausal women appears to be fully capable of alpha 2-PEG production after stimulation with an oral progestogen.

Adenocarcinoma↗
PubMed1987

Immunochemical detection, physicochemical characterization and levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) in seminal plasma of men.

Pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the human uterine endometrium during the luteal phase of the menstrual cycle and early first trimester of pregnancy, has been detected by immunochemical techniques in seminal plasma. Biochemical analysis and immunoblotting has verified that immunoreactive alpha 2-PEG in seminal plasma exhibits properties identical to those of endometrial alpha 2-PEG, i.e. Concanavalin A-binding dimeric glycoprotein of native Mr 56,000, subunit Mr 28,000, average pI 4.7 and of alpha 2-mobility. Concentration of alpha 2-PEG in seminal plasma was 22.13 +/- 2.82 micrograms/ml (mean +/- s.e.m., n = 110) which compared to 12.02 +/- 1.65 micrograms/ml (mean +/- s.e.m., n = 48) found in amniotic fluid at 11-20 weeks of pregnancy, to 4.29 +/- 1.66 micrograms/ml (mean +/- s.e.m., n = 15) in uterine luminal fluid in women during the luteal phase and to 0.245 +/- 0.025 micrograms/ml (mean +/- s.e.m., n = 10) in sera at 10 weeks of pregnancy. This distribution is very different from that observed for pregnancy-associated placentally-derived serum proteins detected in seminal plasma. The source of alpha 2-PEG in seminal plasma is unknown but is unlikely to be the testis because of the normal levels observed in vasectomized men. In the endometrium alpha 2-PEG synthesis and secretion appears to be related to progesterone-dependent differentiation of the glandular epithelium. Therefore these observations suggest that a different mechanism of regulation of the gene for alpha 2-PEG operates in the male reproductive tract.

Chromatography↗
PubMed1989

Immunohistological localization of human pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated beta-lactoglobulin homologue, in the decidua and placenta during pregnancy.

Monoclonal and polyclonal antibodies to pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated human beta-lactoglobulin homologue, were used in an immunohistological technique to determine the cellular localization of this protein in the decidua and placental tissues during pregnancy. During the first trimester the protein was principally localized to the glandular epithelium of the decidua spongiosa region of the endometrium with only weak staining associated with glands of the decidualized decidua compacta region. No significant cellular staining was detected in the decidua capsularis. At term in the decidua of the amniochorion and the placental bed weak staining for alpha 2-PEG was only associated with the epithelium of attenuated glands. No significant staining was detected in the placenta during pregnancy. These results suggest that the epithelium of glands associated with non-decidualized stroma represents the primary source of alpha 2-PEG during the first trimester and that a function of the decidua spongiosa in early pregnancy may be related to production of alpha 2-PEG. The decline in production of alpha 2-PEG during pregnancy is suggested to result from involution of the decidua spongiosa and at term the attenuated glands of the decidua represents the source of alpha 2-PEG.

Decidua↗
PubMed1991

NCI-Black-Reiter (NBR) male rats fail to develop renal disease following exposure to agents that induce alpha-2u-globulin (alpha 2u) nephropathy.

The NCI-Black-Reiter (NBR) rat is the only strain of male rat known not to synthesize the hepatic form of the low molecular weight protein, alpha 2u-globulin. In previous studies, NBR rats were shown not to develop renal disease when exposed to decalin, a compound known to induce alpha 2u-globulin nephropathy in other rat strains. The objective of this study was to show that the presence of alpha 2u-globulin (alpha 2u) is essential for the development of this syndrome in rats exposed to 2,2,4-trimethylpentane (TMP), 1,4-dichlorobenzene (DCB), isophorone (IP), PS-6 unleaded gasoline (UG), and d-limonene (d-L). The induction of alpha 2u-nephropathy in F344 male rats with lindane was used as a positive control and this response was contrasted to male NBR and female F344 rats treated with lindane. Five to seven 11-week-old male NBR rats were exposed to TMP (500 mg/kg/day), DCB (500 mg/kg/day), IP (1000 mg/kg/day), UG (500 mg/kg/day), d-L (1650 mg/kg/day), or lindane (10 mg/kg/day) and five 11-week-old male and female F344 rats were exposed to lindane (10 mg/kg/day) by oral gavage on 4 consecutive days. NBR male and F344 male and female rats gavaged with corn oil were incorporated in the study as vehicle controls. The presence of hyaline droplets was assessed in perfusion-fixed kidneys by staining paraffin sections with Mallory-Heidenhein stain and in GMA sections with Lee's methylene basic blue fuchsin stain. Paraffin sections were also analyzed immunohistochemically for the presence of alpha 2u. Under exposure conditions that clearly induce alpha 2u-nephropathy in male F344 rats, no lesions, hyaline droplets, or alpha 2u were detectable in treated or control male NBR and female F344 rats. It is thus concluded that the presence of alpha 2u is causal to the development of renal disease in rats exposed to TMP, DCB, IP, UG, d-L, and lindane.

Alpha-Globulins↗
PubMed1977

Suppression of tumor-specific cell-mediated cytotoxicity by immunoregulatory alpha-globulin and by immunoregulatory alpha-globulin-like peptides from cancer patients.

The suppression of tumor-specific cell-mediated cytotoxicity by human immunoregulatory alpha-globulin (IRA), by a peptide fraction derived from IRA, and by IRA-like peptides from the serum of cancer patients was studied in a syngeneic murine tumor-host system. Splenic lymphocytes from tumor-immunized mice were cytotoxic specific tumor cells in vitro as measured by the [125]-iododeoxyuridine release microcytotoxicity assay. However, this effect was significantly depressed if 1.25 to 5 mg of IRA per ml were added to the cultures. Pooled lyophilized normal human serum protein was inactive. IRA peptide and IRA-like peptide fractions from cancer patients were also highly suppressive of cell-mediated cytotoxicity at much lower concentrations (0.05 to 0.5 mg/ml). Control human serum peptide, which failed to inhibit the induction of hemolytic plaque-forming cells in sheep erythrocyte-injected mice, had no effect on cell-mediated cytotoxicity. IRA and IRA-like peptide fractions were not cytotoxic to the effector lymphocytes or to the target cells at the concentrations used.

Alpha-Globulins↗