Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The early cellular and molecular changes in the Solt-Farber model of hepatocarcinogenesis with and without initiation was studied by using histochemical, immunohistochemical, and in situ hybridization techniques. Increased cellularity was observed in the periductal space in both models 32 to 56 h after partial hepatectomy. These periductal cells and Ito cells were the only cells that became labeled with tritiated thymidine in the uninitiated liver model. Forty-five to 60% of the labeled periductal cells were positive for gamma-glutamyltranspeptidase. From the periductal area the cells that were positive for antibody raised against oval cells (OV-6) infiltrated into liver parenchyma and were followed by desmin-positive Ito cells. The number of Ito cells in the uninitiated model 6 days after partial hepatectomy was 3.5 times higher in the area occupied by oval cells than elsewhere in the liver. The first alpha-fetoprotein (AFP)-positive cells appeared either as individual cells or as pseudoductal formations 32 or 56 h after partial hepatectomy at the periphery of the periductal space in both initiated and uninitiated animals. A combination of in situ and immunohistochemistry revealed that the OV-6-positive cells were AFP positive, whereas desmin-positive cells were AFP negative. Glutathione S-transferase P (GST-P) transcripts could be found mainly in OV-6-positive oval cells. Bile duct cells were positive for GST-P and negative for transforming growth factor beta 1, whereas cells in the periductal space were positive for both of these transcripts. The GST-P-positive early preneoplastic lesions showed a similar distribution pattern as that of oval cells; the preexisting hepatocytes became trapped between small basophilic hepatocytes that showed either irregular or pseudoalveolar arrangement. This raises the question as to whether cells which are stem cell-like are among the target cells in the Solt-Farber model of hepatocarcinogenesis. Proliferation of transforming growth factor beta 1-producing, desmin-positive cells (Ito cells) and multipotent oval cells in a close proximity to each other indicates an intricate relationship between Ito cells and oval cells in liver that warrants further investigation.
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PMID:Cellular and molecular changes in the early stages of chemical hepatocarcinogenesis in the rat. 169 60

The muscle-specific intermediate filament protein desmin is up-regulated during skeletal muscle differentiation. When myoblasts leave the cell cycle and fusion into multinucleated myotubes starts, genes associated with myogenesis become activated. The activation is believed to be mediated by the muscle-specific determination factors. We present evidence that both MyoD and myogenin are able to activate the transcription of the hamster desmin gene. A proximal promoter fragment of 89 base pairs is sufficient for this transactivation process. The single E-box in this region is essential for desmin promoter activity in mouse C2 skeletal muscle cells and upon co-transfection of a myogenin expression vector also in human primary fibroblasts. Mutation of this MyoD binding site abrogates desmin transcription, and transactivation of the promoter no longer occurs. By using gel electrophoretic mobility shift assays, we were able to demonstrate that nuclear proteins from C2 muscle cells and myogenin/E12 glutathione S-transferase fusion proteins are able to bind to the functional E-box consensus sequence. A second E-box, situated in a more upstream regulatory region, which also binds to purified Helix-Loop-Helix proteins in vitro is only moderately affected by site-directed in vitro mutagenesis.
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PMID:A proximal promoter element in the hamster desmin upstream regulatory region is responsible for activation by myogenic determination factors. 827 97

Abnormal smooth muscle contraction may contribute to diseases such as asthma and hypertension. Alterations to myosin light chain kinase or phosphatase change the phosphorylation level of the 20-kDa myosin regulatory light chain (MRLC), increasing Ca2+ sensitivity and basal tone. One Rho family GTPase-dependent kinase, Rho-associated kinase (ROK or p160(ROCK)) can induce Ca2+-independent contraction of Triton-skinned smooth muscle by phosphorylating MRLC and/or myosin light chain phosphatase. We show that another Rho family GTPase-dependent kinase, p21-activated protein kinase (PAK), induces Triton-skinned smooth muscle contracts independently of calcium to 62 +/- 12% (n = 10) of the value observed in presence of calcium. Remarkably, PAK and ROK use different molecular mechanisms to achieve the Ca2+-independent contraction. Like ROK and myosin light chain kinase, PAK phosphorylates MRLC at serine 19 in vitro. However, PAK-induced contraction correlates with enhanced phosphorylation of caldesmon and desmin but not MRLC. The level of MRLC phosphorylation remains similar to that in relaxed muscle fibers (absence of GST-mPAK3 and calcium) even as the force induced by GST-mPAK3 increases from 26 to 70%. Thus, PAK uncouples force generation from MRLC phosphorylation. These data support a model of PAK-induced contraction in which myosin phosphorylation is at least complemented through regulation of thin filament proteins. Because ROK and PAK homologues are present in smooth muscle, they may work in parallel to regulate smooth muscle contraction.
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PMID:Different molecular mechanisms for Rho family GTPase-dependent, Ca2+-independent contraction of smooth muscle. 972 79

Polycystin-1, the protein defective in a majority of patients with autosomal dominant polycystic kidney disease, is a ubiquitously expressed multi-span transmembrane protein of unknown function. Subcellular localization studies found this protein to be a component of various cell junctional complexes and to be associated with the cytoskeleton, but the specificity and nature of such associations are not known. To identify proteins that interact with the polycystin-1 C-tail (P1CT), this segment was used as bait in a yeast two-hybrid screening of a kidney epithelial cell library. The intermediate filament (IF) protein vimentin was identified as a strong polycystin-1-interacting partner. Cytokeratins K8 and K18 and desmin were also found to interact with P1CT. These interactions were mediated by coiled-coil motifs in polycystin-1 and IF proteins. Vimentin, cytokeratins K8 and K18, and desmin also bound directly to P1CT in GST pull-down and in in vitro filament assembly assays. Two observations confirmed these interactions in vivo: (i) a cell membrane-anchored form of recombinant P1CT decorated the IF network and was found to associate with the cytoskeleton in detergent-solubilized cells and (ii) endogenous polycystin-1 distributed with IF at desmosomal junctions. Polycystin-1 may utilize this association for structural, storage, or signaling functions.
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PMID:Polycystin-1 interacts with intermediate filaments. 1158 Dec 69

In vertebrate skeletal muscle, ultrastructural studies have suggested that the Z-line and extracellular intermediate filaments are linked, although a structural basis for this has remained elusive. We searched for potential novel ligands of the Z-line portion of nebulin by a yeast two-hybrid (Y2H) approach. This identified that the nebulin modules M160 to M170 interact with desmin. In desmin, deletion series experiments assigned a 19-kDa central coiled-coil domain as the nebulin-binding site. The specific interactions of nebulin and desmin were confirmed in vitro by GST pull-down experiments. In situ, the nebulin modules M176 to M181 colocalize with desmin in a Z-line-associated, striated pattern as shown by immunofluorescence studies. Our data are consistent with a model that desmin attaches directly to the Z-line through its interaction with the nebulin repeats M163-M170. This interaction may link myofibrillar Z-discs to the intermediate filament system, thereby forming a lateral linkage system which contributes to maintain adjacent Z-lines in register.
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PMID:Molecular dissection of the interaction of desmin with the C-terminal region of nebulin. 1206 39

The immunohistochemistry of 11 sclerosing stromal tumors (SSTs), 11 fibromas, and 5 thecomas was studied to determine criteria for the assessment of 5 densely sclerotic, calcified ovarian tumors of uncertain diagnosis occurring in young women. The results indicate that the staining pattern for alpha glutathione S-transferase can be used to distinguish SSTs, fibromas, and thecomas. CD34, by highlighting the vascular pattern and density, can be used to distinguish between SSTs and other tumors in the thecoma-fibroma group. Alpha-inhibin and calretinin mirrored the alpha glutathione S-transferase staining. Vimentin, smooth muscle actin, and muscle specific actin were generally positive, but desmin was negative in all but one tumor. These results suggest that at least four of the five tumors of uncertain diagnosis were SSTs that had undergone end-stage sclerosis and calcification.
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PMID:Sclerosing stromal tumors, thecomas, and fibromas of the ovary: an immunohistochemical profile. 1209 May 94

In Triton-skinned phasic ileal smooth muscle, constitutively active recombinant p21-activated kinase (PAK3) has been shown to induce Ca(2+)-independent contraction, which is accompanied by phosphorylation of caldesmon and desmin (Van Eyk JE, Arrell DK, Foster DB, Strauss JD, Heinonen TY, Furmaniak-Kazmierczak E, Cote GP, and Mak AS. J Biol Chem 273: 23433-23439, 1998). In the present study, we investigated whether PAK has a broad impact on smooth muscle in general by testing the hypothesis that PAK induces Ca(2+)-independent contractions and/or Ca(2+) sensitization in tonic airway smooth muscle and that the process is mediated via phosphorylation of caldesmon. In the absence of Ca(2+) (pCa > 9), constitutively active glutathione-S-transferase-murine PAK3 (GST-mPAK3) caused force generation of Triton-skinned canine tracheal smooth muscle (TSM) fibers to approximately 40% of the maximal force generated by Ca(2+) at pCa 4.4. In addition, GST-mPAK3 enhanced Ca(2+) sensitivity of contraction by increasing force generation by 80% at intermediate Ca(2+) concentrations (pCa 6.2), whereas it had no effect at pCa 4.4. Catalytically inactive GST-mPAK3(K297R) had no effect on force production. Using antibody against one of the PAK-phosphorylated sites (Ser(657)) on caldesmon, we showed that a basal level of phosphorylation of caldesmon occurs at this site in skinned TSM and that PAK-induced contraction was accompanied by a significant increase in the level of phosphorylation. Western blot analyses show that PAK1 is the predominant PAK isoform expressed in murine, rat, canine, and porcine TSM. We conclude that PAK causes Ca(2+)-independent contractions and produces Ca(2+) sensitization of skinned phasic and tonic smooth muscle, which involves an incremental increase in caldesmon phosphorylation.
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PMID:Calcium-independent contraction and sensitization of airway smooth muscle by p21-activated protein kinase. 1251 68

GSTs are uncommon mesenchymal tumors of the stomach. The evaluation of malignancy is difficult and their histogenesis is controversial. Recently a relationship to the pacemaker interstitial cells of Cajal (ICC) has been suggested because GSTs, like the ICC express CD117 (C-KIT protein). Some authors, like Miettinen in one of his studies, consider the CD117 positivity as part of the definition of GSTs. The purpose of this paper is to present two cases of GST with immunohistochemical study confirming the diagnosis of GST; the immunoreactivity of these two tumors is positive for CD117 and negative for protein S-100, actine and desmin. A review of the clinicopathologic, the immunohistochemical features, the prognostic factors and novelties in treatment will be presented.
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PMID:[Gastric stromal tumors. Presentation of two cases with immunohistochemical study. Review of the literature]. 1511 53

To identify the mechanisms underlying muscle aging, we have undertaken a high-resolution differential proteomic analysis of gastrocnemius muscle in young adults, mature adults, and old LOU/c/jall rats. Two-dimensional gel electrophoresis and subsequent MALDI-ToF mass spectrometry analyses led to the identification of 40 differentially expressed proteins. Strikingly, most differences characterized old (30-month) animals, whereas young (7-month) and mature (18-month) adults exhibited similar patterns of expression. Important modifications in contractile (actin, myosin light-chains, troponins-T) and cytoskeletal (desmin, tubulin) proteins, and in essential regulatory proteins (gelsolin, myosin binding proteins, CapZ-beta, P23), likely account for dysfunctions in old muscle force generation and speed of contraction. Other features support decreases in cytosolic (triose-phosphate isomerase, enolase, glycerol-3-P dehydrogenase, creatine kinase) and mitochondrial (isocitrate dehydrogenase, cytochrome-c oxidase) energy metabolisms. Muscle aging is often associated with increased oxidative stress. Accordingly, we observed differential regulation of molecular chaperones (hsp20, hsp27, reticuloplasmin ER60) and of proteins implicated in reactive aldehyde detoxification (aldehyde dehydrogenase, glutathione transferase, glyoxalase). We further noticed up-regulation of proteins involved in transcriptional elongation (RNA capping protein) and RNA-editing (Apobec2). Most of these proteins were previously unrecognized as differentially expressed in old muscles, and they represent novel starting points for elucidating the mechanisms of muscle aging.
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PMID:Differential proteome analysis of aging in rat skeletal muscle. 1583 15

Benign (n=33) and malignant metastasizing (n=1) granulosa cell tumours (GCTs) from 34 mares aged 3-21 years, and normal (control) ovaries from nine mares aged 3-10 years, were examined histologically and immunohistochemically (for inhibin alpha, glutathione S-transferase alpha [GSTalpha], c-erbB-2 oncoprotein [cerb], cytokeratin, vimentin, desmin and alpha-actin), the results being related where appropriate to clinical signs and endocrinological data. Availability permitting, serum samples from GCT-affected mares before and several weeks after ovariectomy were examined for the following hormones: oestradiol, progesterone and testosterone (by radioimmunoassay); and inhibin B (by a cross-reactive ELISA). Histological examination revealed that the GCTs were predominantly well differentiated neoplasms. The metastasizing GCT differed immunohistochemically from the benign GCTs in respect of the expression patterns of vimentin, cerb and GSTalpha in the granulosa cells. A notable feature was the presence of Leydig-like cells in mares with stallion-like behaviour or elevated serum testosterone, or both. GSTalpha immunolabelling indicated that the Leydig-like cells were potential producers of steroid hormone. From the immunohistochemical and endocrinological findings it was concluded that GCTs produce abnormally high concentrations of inhibin, which reduce the release of follicle-stimulating hormone, leading to atrophy of the contralateral ovary-a finding in 27 of the mares.
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PMID:Histomorphological and immunohistochemical characterization of equine granulosa cell tumours. 1741 35


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