BACKGROUND: Gamma-glutamyltransferase (GGT) is a well-known laboratory biomarker. In spite of high concentration and the possible biomedical importance of estimating GGT in human seminal plasma (hSP), it has not been widely explored in reproductive physiology. This study aimed to complement existing data on its diversity, previously obtained on seminal extracellular vesicles, by analyzing matched soluble fraction of hSP. The GGT-associated patterns of selected glycoproteins were analyzed in order to establish an adjunct referent parameter for differentiation between known high molecular mass forms of GGT. Getting insight into distinct GGT-associated glycoprotein patterns should contribute to define them together as possible multimarkers. METHODS: GGT forms in soluble, membrane-free-fraction isolated form hSP of normozoospermic men were analyzed using gel filtration and lectin blotting using WGA (wheat germ agglutinin) and Con A (concanavalin A). RESULTS: Widely distributed GGT (with two to three partially resolved peaks), which may correspond to high molecular mass aggregates, were detected. GGT-associated patterns of selected glycoproteins (at position of big, medium, and small-GGT) all comprised high molecular mass WGA-reactive smears, but differed in the presence of Con A-reactive glycans, as well as mucin-associated antigens CA19-9 and CA125. CONCLUSIONS: GGT contributes to several molecular patterns that differ between the soluble and extracellular vesicle fractions of hSP. Their glycobiochemical heterogeneity is due to difference in the presence of distinct sialylated and mannosylated glycans. Moreover, GGT-associated glycoprotein patterns differentiate between high molecular mass forms of GGT in the soluble fraction of hSP. They hold promise as possible targets for increasing biomarker potential of GGT.

• Klíčová slova
• CA125, CA19-9, gamma-glutamyltransferase, human seminal plasma, sialylated glycans,
• MeSH
• biologické markery * metabolismus   MeSH
• dospělí MeSH
• gama-glutamyltransferasa * metabolismus   MeSH
• glykoproteiny * metabolismus   MeSH
• lidé MeSH
• sperma * metabolismus   chemie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery * MeSH
• gama-glutamyltransferasa * MeSH
• glykoproteiny * MeSH

Gamma-glutamyltransferase (GGT) hydrolyses gamma-glutamylated peptides, including glutathione and transports amino acids into the cells. The enzyme is up-regulated in some tumors, especially those with a higher degree of malignancy and resistance to cytostatics. In this study we examined the effects of Cisplatin (1.6 x 10(-5)M) on the activity of GGT in astrocytic C6 glioma cells in cultures monitored for growth, morphology and differentiation. Initially (24 h), the drug inhibited cell division and later (96 h), it caused apoptotic death of about half of the population. The more resistant and surviving cells became hypertrophic and more differentiated, as indicated by their larger size and higher protein content, including the maturation- specific GFAP. In addition, the activity of GGT was significantly elevated in these cells at 48 h and onwards. At 96 h, the biochemically determined enzyme activity was between 230% and 330% above the controls. Compared to the protein content, the GGT activity started to increase later (48 h) but it grew steeper towards 72-96 h. Similarly, histochemical analysis revealed a manifold increase in the number of GGT+ cells in the population and higher intensity of staining per cell from at 48 h and onwards. The study showed that the transformed astrocytic cells can up-regulate GGT activity as part of an adaptation and/or, survival-enhancing reaction triggered by Cisplatin.

• MeSH
• apoptóza MeSH
• astrocyty cytologie   patologie   MeSH
• buněčná diferenciace MeSH
• buněčné dělení MeSH
• časové faktory MeSH
• cisplatina farmakologie   MeSH
• gama-glutamyltransferasa biosyntéza   MeSH
• gliom metabolismus   patologie   MeSH
• gliový fibrilární kyselý protein metabolismus   MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové buňky kultivované MeSH
• protinádorové látky farmakologie   MeSH
• průtoková cytometrie MeSH
• upregulace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cisplatina MeSH
• gama-glutamyltransferasa MeSH
• gliový fibrilární kyselý protein MeSH
• protinádorové látky MeSH

The localization of aminopeptidase M (APM), aminopeptidase A (APA) and gama-glutamyltransferase (GGT) activity was studied at light microscope level in the nasal cavity organs of the laboratory rodents (rat, mouse, guinea pig) and human foetuses. All the enzymes were demonstrated histochemically in chloroform-acetone pretreated cryostat sections with application of azocoupling methods (5, 9). These membrane-bound aminopeptidases may participate in the metabolism of peptides in the nasal cavity. They have specific roles as modulators of growth and differentiation of the epithelial cells. The results revealed differences in enzyme patterns between olfactory and respiratory epithelium. GGT seemed to be present only in respiratory epithelium and in the ducts of Bowman's glands. Activity of APM and APA was found mostly in the fibrocytes which adhered to the basal membrane of the epithelium and glands.

• MeSH
• aminopeptidasy analýza   MeSH
• antigeny CD13 analýza   MeSH
• gama-glutamyltransferasa analýza   MeSH
• glutamylaminopeptidasa MeSH
• histocytochemie MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• morčata MeSH
• myši MeSH
• nosní dutina enzymologie   MeSH
• plod enzymologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• morčata MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminopeptidasy MeSH
• antigeny CD13 MeSH
• gama-glutamyltransferasa MeSH
• glutamylaminopeptidasa MeSH

OBJECTIVE: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. STUDY DESIGN: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. RESULTS: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. CONCLUSIONS: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.

• Klíčová slova
• autoimmune, cholestasis, juvenile, surrogate endpoint, treatment,
• MeSH
• analýza rozptylu MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dítě MeSH
• gama-glutamyltransferasa krev   MeSH
• jaterní testy MeSH
• kohortové studie MeSH
• kyselina ursodeoxycholová terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• neúspěšná terapie MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• sklerozující cholangitida krev   farmakoterapie   MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• gama-glutamyltransferasa MeSH
• kyselina ursodeoxycholová MeSH

Gamma-glutamyltransferase (GGT), a marker of liver disease, has been shown to be associated with increased risk of diabetes and relative insulin secretion deficiency. However, the mechanism of hepatic Ggt regulation has not been explored fully. In this study, we made a concerted effort to understand the mechanism by investigating the effects of acetylation of histones H3 and H4, and bindings of histone acetyltransferases, CREB binding protein (CBP) and p300, at the Ggt promoter on the regulation of the expression of Ggt gene in the livers of streptozotocin (STZ)-induced moderate hypoinsulinemia rat model. The rats treated with STZ showed remarkably higher serum GGT level and hepatic Ggt/GGT expression than the untreated control rats. Furthermore, the acetylation of histones H3 and H4, and the binding of CBP not p300 at the Ggt promoter regions were significantly higher in the livers of STZ rats than those of the control rats. These results suggest that an enhanced hepatic expression of Ggt is associated with increased acetylation of histones H3 and H4 and CBP binding at the Ggt promoter in STZ-induced moderate hypoinsulinemic rats.

• MeSH
• acetylace MeSH
• experimentální diabetes mellitus enzymologie   genetika   MeSH
• gama-glutamyltransferasa biosyntéza   genetika   MeSH
• histonacetyltransferasy metabolismus   MeSH
• histony metabolismus   MeSH
• játra enzymologie   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• promotorové oblasti (genetika) MeSH
• protein p300 asociovaný s E1A metabolismus   MeSH
• protein vázající CREB metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CREBBP protein, human MeSH Prohlížeč
• Crebbp protein, rat MeSH Prohlížeč
• Ep300 protein, rat MeSH Prohlížeč
• gama-glutamyltransferasa MeSH
• histonacetyltransferasy MeSH
• histony MeSH
• protein p300 asociovaný s E1A MeSH
• protein vázající CREB MeSH

• MeSH
• alkoholismus diagnóza   MeSH
• dospělí MeSH
• gama-glutamyltransferasa krev   MeSH
• klinické enzymatické testy * MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• gama-glutamyltransferasa MeSH

• MeSH
• druhý trimestr těhotenství * MeSH
• gama-glutamyltransferasa analýza   MeSH
• lidé MeSH
• plodová voda enzymologie   MeSH
• referenční hodnoty MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• gama-glutamyltransferasa MeSH

• MeSH
• gama-glutamyltransferasa krev   MeSH
• klinické enzymatické testy * MeSH
• lidé MeSH
• nádory jater diagnóza   sekundární   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• gama-glutamyltransferasa MeSH

• MeSH
• alkoholické nemoci jater diagnóza   MeSH
• diferenciální diagnóza MeSH
• gama-glutamyltransferasa krev   MeSH
• izoenzymy krev   MeSH
• klinické enzymatické testy * MeSH
• lidé MeSH
• nemoci jater diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• gama-glutamyltransferasa MeSH
• izoenzymy MeSH

• MeSH
• gama-glutamyltransferasa analýza   MeSH
• klinické enzymatické testy MeSH
• lidé MeSH
• nemoci plodu diagnóza   MeSH
• plodová voda enzymologie   MeSH
• prenatální diagnóza * MeSH
• těhotenství MeSH
• vrozené vady diagnóza   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• gama-glutamyltransferasa MeSH