Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methamphetamine (METH) is an abusive psychostimulant that induces neuronal cell death/degeneration in experimental animals and humans. METH-induced apoptosis in rat pheochromocytoma cells was utilized to study the neurotoxic mechanism. During METH intoxication, we found that peroxiredoxins and thioredoxins/thioredoxin reductases (peroxiredoxin reducing systems) which are known to prevent oxidative stress and apoptosis were differentially downregulated and upregulated, respectively. We also found not only the free radicals but also the oxidative forms of peroxiredoxin and thioredoxin were increased, indicating the dysfunction of these enzymes. Thus, METH-induced differential regulation and oxidation of peroxiredoxins and thioredoxin may be an important mechanism for apoptosis.
 ...
PMID:Methamphetamine downregulates peroxiredoxins in rat pheochromocytoma cells. 1721 Jan 25

The genome of the cyanobacterium Anabaena PCC 7120 encodes seven polypeptides showing sequence similarities with peroxiredoxins (Prx-s). One of them, prxQ-A (alr2503), which encodes a Prx Q homologue, is located in the same gene cluster as pkn22, which encodes a Ser/Thr kinase. Here we report that the pkn22-knockout mutant (Mp22) is sensitive to oxidative stress because it fails to synthesize PrxQ-A; the expression of prxQ-A is significantly induced under oxidative stress conditions. The hypersensitivity of the Mp22 mutant to oxidative stress was restored by inducing the expression of the prxQ-A gene in trans. The recombinant PrxQ-A protein shows antioxidant activity protecting the DNA from being degraded by reactive oxygen species, catalyzes the reduction of H2O2 in the presence of DTT, and shows thioredoxin-dependent peroxidase activity in vitro. The conserved Cys47 residue is the peroxide oxidation site, since the replacement of Cys47 by a Ser residue completely abolished the peroxidase activity. All these data suggest that PrxQ-A may efficiently protect this organism from oxidative stress.
 ...
PMID:PrxQ-A, a member of the peroxiredoxin Q family, plays a major role in defense against oxidative stress in the cyanobacterium Anabaena sp. strain PCC7120. 1721 Apr 55

The filamentous cyanobacteria of the genus Nostoc are globally distributed, phenotypically complex organisms, capable of cellular differentiation and of forming symbiotic associations with a wide range of plants. To further our understanding of these processes and functions, the proteome of photoautotrophically and diazotrophically grown Nostoc sp. PCC 73102 (N. punctiforme) cells was examined. Extracted proteins were separated into membrane and soluble protein fractions and analysed using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The analysis led to the identification of 82 proteins that could be divided into 12 functional categories. Significantly, 65 of these proteins have not been previously documented in the Nostoc proteome. Many of the proteins identified were readily recognized as housekeeping proteins involved in carbon, nitrogen and energy metabolism, but a number of proteins related to stress, motility, secretion and post-translational modifications were also identified. Ten unclassified proteins were also detected, representing potential novel functions. These proteins were highly expressed, suggesting that they play key roles during photoautotrophic and diazotrophic growth. Nineteen of the proteins expressed under the growth conditions examined contained putative thioredoxin (Trx) targets, a motif that functions in redox regulation via redox equivalent mediators and is known to be significant in a wide range of biological processes. These observations contribute to our understanding of the complex Nostoc life cycle.
 ...
PMID:Proteomic analyses of the photoauto- and diazotrophically grown cyanobacterium Nostoc sp. PCC 73102. 1725 33

The IdiC protein (iron deficiency induced protein C) is encoded by orf5 (now called idiC), which is part of the iron-responsive idiB operon of Synechococcus elongatus PCC 7942. The 20.5 kDa IdiC protein has a putative transmembrane helix and belongs to the thioredoxin (TRX)-like [2Fe-2S] ferredoxin family. IdiC has the highest similarity to the peripheral subunit NuoE of the Escherichia coli NDH-1 complex. IdiC expression increased under iron starvation and also in the late growth phase, representing growth conditions, which favor photosynthetic cyclic and respiratory electron transport over photosynthetic linear electron transport from water to NADP+. Attempts to insertionally inactivate the idiC gene generated merodiploid mutants with a strongly reduced IdiC content (mutant MuD) but no IdiC-free mutant. Thus, IdiC seems to be an essential protein for the viability of S. elongatus under the used experimental conditions. Comparative analyses of S. elongatus wild type (WT) and mutant MuD showed that under iron limitation in WT and MuD the amount of the reaction center proteins PsbA and PsaA/B was highly reduced. MuD had a lower growth rate, chlorophyll content, and photosynthetic O2 evolving activity with bicarbonate as electron acceptor than WT. Immunoblot analyses also showed that in MuD, when grown under iron limitation, the amount of the proteins IdiC and IdiB was greatly reduced as compared to WT. As a consequence of the reduction of the transcription factor IdiB, IdiA and IrpA expression were also decreased. In addition, the IsiA protein concentration was lower in MuD than in WT, although the isiA mRNA was equally high in MuD and WT. Another significant difference was the lower expression of the ferredoxin:NADP+ oxidoreductase in mutant MuD under iron limitation compared to WT. A possible function of the protein IdiC in cyclic electron transport around photosystem I and/or in respiratory electron transport will be discussed.
 ...
PMID:Characterization of the putative iron sulfur protein IdiC (ORF5) in Synechococcus elongatus PCC 7942. 1769 Sep 95

Cysteine dithiol/disulphide exchange forms the molecular basis for regulation of a wide variety of enzymatic activities and for transduction of cellular signals. Thus, the search for proteins with reactive, accessible cysteines is expected to contribute to the unravelling of new molecular mechanisms for enzyme regulation and signal transduction. Several methods have been designed for this purpose taking advantage of the interactions between thioredoxins and their protein substrates. Thioredoxins comprise a family of redox-active enzymes, which catalyse reduction of protein disulphides and sulphenic acids. Due to the inherent practical difficulties associated with studies of membrane proteins these have been largely overlooked in the many proteomic studies of thioredoxin-interacting proteins. In the present work, we have developed a procedure to isolate membrane proteins interacting with thioredoxin by binding in situ to a monocysteinic His-tagged thioredoxin added directly to the intact membranes. Following fractionation and solubilisation of the membranes, thioredoxin target proteins were isolated by Ni-affinity chromatography and 2-DE SDS-PAGE under nonreducing/reducing conditions. Applying this method to total membranes, including thylakoid and plasma membranes, from the cyanobacterium Synechocystis sp. PCC 6803 we have identified 50 thioredoxin-interacting proteins. Among the 38 newly identified thioredoxin targets are the ATP-binding subunits of several transporters and members of the AAA-family of ATPases.
 ...
PMID:Membrane proteins from the cyanobacterium Synechocystis sp. PCC 6803 interacting with thioredoxin. 1792 17

The genome of Synechococcus elongatus PCC 7942 encodes six peroxiredoxins (Prx). Single genes are present each for a 1-Cys Prx and a 2-Cys Prx, while four genes code for PrxQ-like proteins (prxQ-A1, -A2, -A3 and B). Their transcript accumulation varies with growth conditions in a gene-specific manner (Stork et al. in J Exp Bot 56:3193-3206, 2005). To address their functional properties, members of the prx gene family were produced as recombinant proteins and analysed for their peroxide detoxification capacity and quaternary structure by size exclusion chromatography. Independent of the reduction state, the 2-Cys Prx separated as oligomer, the 1-Cys Prx as dimer and the PrxQ-A1 as monomer. PrxQ-A2 was inactive in our assays, 1-Cys Prx activity was unaffected by addition of TrxA, while all others were stimulated to a variable extent by addition of E. coli thioredoxin. Sensitivity towards cumene hydroperoxide treatment of E. coli BL21 cells expressing the cyanobacterial PrxQ-A1 to A3 proteins was greatly reduced, while expression of the other Prx had no effect. The study shows differentiation of Prx functions in S. elongatus PCC 7942 which is discussed in relation to potential roles in site- and stress-specific defence.
 ...
PMID:Functional characterisation of the peroxiredoxin gene family members of Synechococcus elongatus PCC 7942. 1897 76

The thioredoxin (Trx) system, comprising Trx, the selenoprotein thioredoxin reductase (TrxR), and NADPH, functions as an antioxidant system. Trx has various biological activities including growth control and anti-apoptotic properties, and the Trx system offers a target for the development of drugs to treat and/or prevent cancer. We evaluated the role of TrxR inhibition in the release of arachidonic acid (AA), cell toxicity, and intracellular signaling pathways in L929 mouse fibrosarcoma cells. Treatment with 1-chloro-2,4-dinitrobenzene (DNCB, an inhibitor of TrxR) under conditions involving limited inhibition of TrxR activity in cells, released AA before causing cytotoxicity. Treatment with an inhibitor of p38 kinase, a downstream enzyme of the apoptosis signal-regulating kinase 1 pathway, and pyrrophenone (an inhibitor of alpha-type cytosolic phospholipase A(2), cPLA(2)alpha) partially but significantly decreased the DNCB-induced release of AA and cell death. The responses were much weaker in cPLA(2)alpha knockdown L929 cells. Exogenously added AA showed cytotoxicity. DNCB increased intracellular reactive oxygen species (ROS) levels, and butylated hydroxyanisole (an antioxidant) reduced DNCB-induced ROS formation and cell toxicity but not the phosphorylation of p38 kinase and release of AA. Auranofin, another inhibitor of TrxR having a different formula, released AA resulting in toxicity in L929 cells. DNCB caused the release of AA and cytotoxicity in A549 human lung carcinoma cells, and caused p38 kinase-dependent toxicity in PC12 rat pheochromocytoma cells. Our data suggest that a dysfunctional Trx system triggers multiple signaling pathways, and that the AA released by cPLA(2)alpha-dependent and -independent pathways is important to cytotoxicity. J. Cell. Physiol. 219: 606-616, 2009. (c) 2009 Wiley-Liss, Inc.
 ...
PMID:Cytotoxicity induced by inhibition of thioredoxin reductases via multiple signaling pathways: role of cytosolic phospholipase A(2)alpha-dependent and -independent release of arachidonic acid. 1917 71

Light-dependent disulphide/dithiol exchange catalysed by thioredoxin is a classical example of redox regulation of chloroplast enzymes. Recent proteome studies have mapped thioredoxin target proteins in all chloroplast compartments ranging from the envelope to the thylakoid lumen. Progress in the methodologies has made it possible to identify which cysteine residues interact with thioredoxin and to tackle membrane-bound thioredoxin targets. To date, more than hundred targets of thioredoxin and glutaredoxin have been found in plastids from Arabidopsis, spinach, poplar and Chlamydomonas reinhardtii. Thioredoxin-mediated redox control appears to be a feature of the central pathways for assimilation and storage of carbon, sulphur and nitrogen, as well as for translation and protein folding. Cyanobacteria are oxygenic photosynthetic prokaryotes, which presumably share a common ancestor with higher plant plastids. As in chloroplasts, cyanobacterial thioredoxins receive electrons from the photosynthetic electron transport, and thioredoxin-targeted proteins are therefore highly interesting in the context of acclimation of these organisms to their environment. Studies of the unicellular model cyanobacterium Synechocystis sp. PCC 6803 revealed 77 thioredoxin target proteins. Notably, the functions of all these thioredoxin targets highlight essentially the same processes as those described in chloroplasts suggesting that thioredoxin-mediated redox signalling is equally significant in oxygenic photosynthetic prokaryotes and eukaryotes.
 ...
PMID:Disulphide proteomes and interactions with thioredoxin on the track towards understanding redox regulation in chloroplasts and cyanobacteria. 1918 68

Arsenic resistance in Synechocystis sp. strain PCC 6803 is mediated by an operon of three genes in which arsC codes for an arsenate reductase with unique characteristics. Here we describe the identification of two additional and nearly identical genes coding for arsenate reductases in Synechocystis sp. strain PCC 6803, which we have designed arsI1 and arsI2, and the biochemical characterization of both ArsC (arsenate reductase) and ArsI. Functional analysis of single, double, and triple mutants shows that both ArsI enzymes are active arsenate reductases but that their roles in arsenate resistance are essential only in the absence of ArsC. Based on its biochemical properties, ArsC belongs to a family that, though related to thioredoxin-dependent arsenate reductases, uses the glutathione/glutaredoxin system for reduction, whereas ArsI belongs to the previously known glutaredoxin-dependent family. We have also analyzed the role in arsenate resistance of the three glutaredoxins present in Synechocystis sp. strain PCC 6803 both in vitro and in vivo. Only the dithiolic glutaredoxins, GrxA (glutaredoxin A) and GrxB (glutaredoxin B), are able to donate electrons to both types of reductases in vitro, while GrxC (glutaredoxin C), a monothiolic glutaredoxin, is unable to donate electrons to either type. Analysis of glutaredoxin mutant strains revealed that only those lacking the grxA gene have impaired arsenic resistance.
 ...
PMID:The glutathione/glutaredoxin system is essential for arsenate reduction in Synechocystis sp. strain PCC 6803. 1930 54

Elongation factor G (EF-G), a key protein in translational elongation, was identified as a primary target of inactivation by reactive oxygen species within the translational machinery of the cyanobacterium Synechocystis sp. PCC 6803 (Kojima, K., Oshita, M., Nanjo, Y., Kasai, K., Tozawa, Y., Hayashi, H., and Nishiyama, Y. (2007) Mol. Microbiol. 65, 936-947). In the present study, we found that inactivation of EF-G (Slr1463) by H(2)O(2) was attributable to the oxidation of two specific cysteine residues and formation of a disulfide bond. Substitution of these cysteine residues by serine residues protected EF-G from inactivation by H(2)O(2) and allowed the EF-G to mediate translation in a translation system in vitro that had been prepared from Synechocystis. The disulfide bond in oxidized EF-G was reduced by thioredoxin, and the resultant reduced form of EF-G regained the activity to mediate translation in vitro. Western blotting analysis showed that levels of the oxidized form of EF-G increased under strong light in a mutant that lacked NADPH-thioredoxin reductase, indicating that EF-G is reduced by thioredoxin in vivo. These observations suggest that the translational machinery is regulated by the redox state of EF-G, which is oxidized by reactive oxygen species and reduced by thioredoxin, a transmitter of reducing signals generated by the photosynthetic transport of electrons.
 ...
PMID:Regulation of translation by the redox state of elongation factor G in the cyanobacterium Synechocystis sp. PCC 6803. 1944 82


<< Previous 1 2 3 4 5 6 Next >>