Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.47 (cysteine synthase)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Age-related progressive glomerular sclerosis in the rat is associated with increased expression of tumor necrosis factor-beta1 and increased protein content in the renal cortex, enhanced production of H2O2, in both renal glomeruli and mesangial cells (MCs) cultured from them, as well as augmented glomerular oxidative damage. We have previously shown that tretinoin-treated old male Fischer 344 rats have 30% lower protein content in the renal cortex than control old rats. Here, we report that this effect may depend on the inhibition of the expression of tumor necrosis factor-beta1, a matrigenic cytokine, and osteopontin, a protein with cell adhesive and chemotactic properties. In addition, we show that tretinoin prevents the cytotoxicity of H2O2 in cultured human MCs by increasing both the catalase activity and the reduced glutathione content, which are dose- and time-dependent changes. These increases were not dependent on each other: when these effects were previously inhibited with 3-amino-1,2,4-atriazole or L-buthionine-(S, R)-sulfoximine, respectively, tretinoin still induced the increase of the other noninhibited antioxidant defense. An enhanced gene transcription is the most likely mechanism involved in the tretinoin-induced stimulation of MC antioxidant defense systems because 1) preincubation of MCs with actinomycin D or cycloheximide fully abolished it; 2) tretinoin-incubated MCs showed increased levels of catalase mRNA and gamma-glutamyl-cysteine synthetase (catalytic subunit) mRNA, the latter being the rate-limiting step in de novo reduced glutathione synthesis; and 3) the stability of both mRNA was unchanged by tretinoin. These results show one strategy of protecting renal cells from H2O2-mediated injury based on increasing their antioxidant defenses.
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PMID:Tretinoin prevents age-related renal changes and stimulates antioxidant defenses in cultured renal mesangial cells. 1008 95

A wide spectrum of human lung diseases is characterized by the presence of granulomas. Although understanding of the pathways leading to their development remains incomplete, data from in vitro studies suggest that neutrophils, monocytes, and their secreted products (eg, hydrogen peroxide, H2O2) influence the pathogenesis of pulmonary granulomatous disease through the regulation of local chemokine and cytokine production. Using a well-characterized rat model of glucan-induced pulmonary granulomatous vasculitis, we sought to determine the role of intracellular glutathione (GSH) redox status in the expression of monocyte chemoattractant protein-1 (MCP-1). Previous studies have revealed that vascular wall MCP-1 expression is obligatory for granuloma development and that both neutrophils and hydrogen peroxide are required for MCP-1 induction. Because in vitro expression of MCP-1 is in part mediated by the redox-sensitive transcription factors nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), we studied their activation as a function of varying intracellular GSH redox status in the pathogenesis of glucan-induced pulmonary granulomatosis. Infusion of particulate yeast cell wall glucan into rats resulted in a rapid decrease in intracellular GSH concentrations which was accompanied by the activation of NF-kappaB and AP-1. The pattern of AP-1 and NF-kappaB activation in turn correlated temporally with the expression of MCP-1. Administration of L-buthionine-S, R-sulfoximine, a specific inhibitor of gamma-glutamyl cysteine synthetase, resulted in a significant reduction in intracellular GSH pools. GSH depletion resulted in a more than 100% increase in pulmonary MCP-1 concentrations and increased cytosolic to nuclear translocation of NF-kappaB while having no effect on AP-1 levels. These observations suggest that in the pathogenesis of pulmonary granulomatous disease, intracellular glutathione redox status modulates the expression of MCP-1 through redox-sensitive transcription factors.
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PMID:Intracellular glutathione redox status modulates MCP-1 expression in pulmonary granulomatous vasculitis. 1041 24

Thioredoxin (Trx) is one of the major redox-regulating proteins. It catalyzes dithiol/disulfide exchange reactions and displays many unique intracellular and extracellular activities thereby controlling multiple mammalian cell functions. In the present study we examine the effect of exogenous Trx on the expression of several antioxidant genes in human lens epithelial (HLE B3) cells. mRNA levels for gene expression were monitored by RT-PCR and real-time PCR while protein levels were measured by western blot analysis. We have found that recombinant human Trx (hTrx)-treated HLE B3 cells have a simultaneous increase in mRNA expressions of mitochondrial manganese superoxide dismutase (MnSOD), thioltranferase 1 (TTase 1) or glutaredoxin 1 (Grx1), mitochondrial thioltransferase (TTase 2) or glutaredoxin 2 (Grx2), and thioredoxin peroxidase IV (Prx IV). The increased MnSOD and TTase 1 mRNA expressions were accompanied with their respective increases in protein levels. Other antioxidant genes, including Cu/ZnSOD, catalase, glutathione peroxidase 1 (GPx1), thioredoxin reductase 1 (TrxR1), thioredoxin peroxidase III (Prx III), and gamma-glutamyl cysteine synthetase were not affected. The ability of Trx to induce selectively these antioxidant genes in the absence of oxidative stress suggest a cytokine/growth factor-like new physiological role of hTrx in HLE B3 cells. Our data also provide evidence of a strong antioxidant defense system in HLE B3 cells that can be activated by extracellular hTrx, as well as of a possible link between the thioredoxin (Trx) and glutathione (GSH) redox regulating systems in these cells.
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PMID:Thioredoxin induced antioxidant gene expressions in human lens epithelial cells. 1671 39

The exoproteome of Staphylococcus aureus contains enzymes and virulence factors that are important for host adaptation. We investigated the exoprotein profiles and cytokine/chemokine responses obtained in three different S. aureus-host interaction scenarios by using two-dimensional gel electrophoresis (2-DGE) and two-dimensional immunoblotting (2D-IB) combined with tandem mass spectrometry (MS/MS) and cytometric bead array techniques. The scenarios included S. aureus bacteremia, skin and soft tissue infections (SSTIs), and healthy carriage. By the 2-DGE approach, 12 exoproteins (the chaperone protein DnaK, a phosphoglycerate kinase [Pgk], the chaperone GroEL, a multisensor hybrid histidine kinase, a 3-methyl-2-oxobutanoate hydroxymethyltransferase [PanB], cysteine synthase A, an N-acetyltransferase, four isoforms of elongation factor Tu [EF-Tu], and one signature protein spot that could not be reliably identified by MS/MS) were found to be consistently present in more than 50% of the bacteremia isolates, while none of the SSTI or healthy-carrier isolates showed any of these proteins. By the 2D-IB approach, we also identified five antigens (methionine aminopeptidase [MetAPs], exotoxin 15 [Set15], a peptidoglycan hydrolase [LytM], an alkyl hydroperoxide reductase [AhpC], and a haptoglobin-binding heme uptake protein [HarA]) specific for SSTI cases. Cytokine and chemokine production varied during the course of different infection types and carriage. Monokine induced by gamma interferon (MIG) was more highly stimulated in bacteremia patients than in SSTI patients and healthy carriers, especially during the acute phase of infection. MIG could therefore be further explored as a potential biomarker of bacteremia. In conclusion, 12 exoproteins from bacteremia isolates, MIG production, and five antigenic proteins identified during SSTIs should be further investigated for potential use as diagnostic markers.
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PMID:Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization. 2580 33