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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A gene conferring low-level isoniazid (INH) resistance on Mycobacterium smegmatis was isolated from a cosmid library of the genome of an INH-resistant Mycobacterium bovis strain. The gene had good homology with ahpC, the product of which is a subunit of alkyl hydroperoxide reductase, and also with a family of thiol-specific antioxidant enzymes. A mutation was found in the promoter upon comparison with the equivalent DNA sequence from the INH-sensitive parent strain. Promoter sequences from other INH-sensitive and INH-resistant M. bovis and Mycobacterium tuberculosis strains were sequenced and the mutation was found only in the INH-resistant strains. An INH-resistant M. tuberculosis strain also had an additional mutation in the promoter region. The wild-type promoter and promoters with one and two mutations were ligated into a reporter plasmid containing the lacZ gene. The presence of the first mutation resulted in a sixfold induction of beta-galactosidase activity, and the presence of both mutations caused a 10-fold induction. Increased expression of AhpC may account for some of the INH resistance of strains of the M. tuberculosis complex.
Mol Microbiol 1996 Mar
PMID:ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex. 883 Feb 60

Antioxidants can remove damaging reactive oxygen species produced as by-products of desiccation and respiration during late embryogenesis, imbibition of dormant seeds and germination. We have expressed a protein, PER1, encoded by the Balem (barley aleurone and embryo) transcript previously called B15C, and show it to reduce oxidative damage in vitro. PER1 shares high similarity to a novel group of thiol-requiring antioxidants, named peroxiredoxins, and represents a subgroup with only one conserved cysteine residue (1-Cys). PER1 is the first antioxidant belonging to the 1-Cys subgroup shown to be functionally active, and the first peroxiredoxin of any kind to be functionally described in plants. The steady state level of the transcript, Per1, homologous to a dormancy-related transcript (pBS128) from bromegrass (Bromus secalinus), increases considerably in imbibed embryos from dormant barley (Hordeum vulgare L.) grains. Our investigations also indicate that Per1 transcript levels are dormancy-related in the aleurone layer of whole grains. In contrast to most seed-expressed antioxidants Per1 disappears in germinating embryos, and in the mature aleurone the transcript is down-regulated by the germinating embryo or by gibberellic acid (GA). Our data show that the barley seed peroxiredoxin is encoded by a single Per1 gene. Possible roles of the PER1 peroxiredoxin in barley grains during desiccation, dormancy and imbibition are discussed.
Plant Mol Biol 1996 Sep
PMID:A peroxiredoxin antioxidant is encoded by a dormancy-related gene, Per1, expressed during late development in the aleurone and embryo of barley grains. 891 36

A Dirofilaria immitis cDNA clone encoding a nucleic acid homolog of thioredoxin peroxidase (nDiTPx) was isolated from a fourth-stage larval cDNA library, using serum from dogs vaccinated by chemotherapeutically-abbreviated D. immitis larval infections. The protein encoded by nDiTPx had a predicted molecular mass of 22.1 kDa and the deduced amino acid sequence was homologous to thioredoxin peroxidase-like sequences described in other filarial nematodes, yeast, bacteria and mammals. As is true for other members of this peroxiredoxin family, the nDiTPx-encoded protein had the conserved cysteine near the amino terminus, considered to be essential for enzyme activity. nDiTPx was expressed in E. coli and the resulting recombinant fusion protein was shown to have thioredoxin peroxidase (TPx) activity, by its ability to protect DNA from oxidative-nicking in a metal-catalyzed oxidation system. A polyclonal antibody to the DiTPx fusion protein detected a 22-kDa native protein in D. immitis larval and adult parasite extracts.
Mol Biochem Parasitol 1997 Dec 01
PMID:Molecular cloning, expression and enzymatic activity of a thioredoxin peroxidase from Dirofilaria immitis. 949 51

Parasite-derived antioxidant proteins have been implicated in playing an important role in protection against the oxygen radicals that are generated during aerobic metabolism and in defense against host immune cell attack. Here we report that filarial nematodes include the thioredoxin peroxidase/thiol-specific antioxidant (TPx/TSA) family of antioxidant proteins as part of their complex defense against radical-mediated damage. At the protein level, the TPx/TSA from Brugia malayi (Bm-TPx-1) was approximately 50% identical and approximately 60% similar to TPx/TSAs from mammals, amphibians and yeast. Bm-TPx-1 was also approximately 60% identical to putative TPx proteins from a related filarial nematode, Onchocerca volvulus, and from the free-living nematode Caenorhabditis elegans. That B. malayi may express multiple forms of molecules with TPx/TSA activity was indicated by the identification of a B. malayi gene encoding a second, distinct member of the TPx/TSA family (Bm-tpx-2). Bm-tpx-1 was found to be transcribed in all stages of the parasite present in the mammalian host and the 25 kDa translation product was present in all of the developmental stages studied. The results of immunohistochemical, immunofluorescent and immunoprecipitation studies showed Bm-TPx-1 to be localized in the cells of the hypodermis/lateral chord in adult parasites and not to be present at the surface or in excretory/secretory products. The distribution in the parasite suggests that Bm-TPx-1 may play its major role in countering radicals produced within cells. A recombinant form of Bm-TPx-1 was biologically active and capable of protecting DNA from oxygen radical-mediated damage. Thioredoxin peroxidases may prove to be a critical component in the parasite's defense against injury caused by oxygen radicals derived from endogenous and exogenous sources.
Mol Biochem Parasitol 1998 Mar 15
PMID:Thioredoxin peroxidases from Brugia malayi. 956 15

Random screening of an Onchocerca volvulus third-stage (L3) cDNA library identified a highly abundant cDNA encoding a newly discovered antioxidant enzyme, thioredoxin peroxidase (TPx), a member of the peroxidoxin superfamily. This TPx cDNA (Ov-tpx-2) encodes a polypeptide of 199 amino acid residues with a calculated molecular weight of 21,890 Da. The Ov-tpx-2 cDNA represents roughly 2.5% of the total cDNAs from the L3 cDNA library. The gene was expressed in Escherichia coli and the protein product was shown to have antioxidant activity. Antiserum raised against Ov-TPX-2 recognized a native protein from extracts of both the L3 and adult-stages with a molecular weight of 22 kD. The localization and stage-specificity of Ov-TPX-2 protein was analyzed by immunocytochemistry and immunoelectron microscopy using monospecific antibodies. Expression was detected in late first-stage larvae during development in the vector and increased in intensity during differentiation to the infective L3-stage. The antigen was also detected in post-infective larvae and adult worms. In larvae, Ov-TPX-2 protein was predominantly localized to the hypodermis and cuticle, with additional sites in the hypodermal chords and multivesicular bodies. In adult worms, the primary sites of expression were the uterine epithelium and intestine, with additional labeling of the body wall and cuticle. Developing embryos and microfilariae in utero were bathed in Ov-TPX-2 protein discharged from epithelial cells. These results suggest that Ov-TPX-2 may protect the parasites from being damaged by host-generated oxidative stress and that Ov-TPX-2 protein provides the H2O2-detoxifying activity predicted but not previously identified in filarial parasites. Its highly upregulated expression in infective larvae may aid in parasite establishment following transmission to the definitive host.
Mol Biochem Parasitol 1998 Mar 15
PMID:Thioredoxin peroxidase from Onchocerca volvulus: a major hydrogen peroxide detoxifying enzyme in filarial parasites. 956 16

We have isolated a gene, AtPer1, from the dicotyledon Arabidopsis thaliana, which shows similarity to the 1-cysteine (1-Cys) peroxiredoxin family of antioxidants. In higher plants, members of this group of antioxidants have previously only been isolated from monocotyledons. It has been suggested that seed peroxiredoxins protect tissues from reactive oxygen species during desiccation and early imbibition and/or are involved in the maintenance of/protection during dormancy. AtPer1 expression is restricted to seeds. Despite differences in seed development between monocots and dicots, AtPer1 shows an expression pattern during seed development and germination similar to the dormancy-related transcript Per1 in barley. In situ hybridization identifies AtPer1 as the first aleurone-expressed transcript characterized in developing Arabidopsis seeds. The transcript is also expressed in the embryo. AtPer1 expression in seeds is unaltered in an ABA-deficient mutant (aba-1) during seed development, while expression in seeds of an ABA-insensitive mutant (abi3-1) is reduced. The transcript is not induced in vegetative tissue in response to stress by ABA or drought. AtPer1 transcript levels are correlated to germination frequencies of wildtype seeds, but AtPer1 transcript abundance is not sufficient for expression of dormancy in non-dormant mutants. Hypotheses on peroxiredoxin function are discussed in view of the results presented here.
Plant Mol Biol 1998 Apr
PMID:The expression of a peroxiredoxin antioxidant gene, AtPer1, in Arabidopsis thaliana is seed-specific and related to dormancy. 958 97

As a consequence of aerobic metabolism, trypanosomatids are exposed to reactive oxygen intermediates such as superoxide, hydrogen peroxide and the hydroxyl radical. Metabolism of hydrogen peroxide in Crithidia fasciculata is accomplished by three distinct proteins, tryparedoxin, tryparedoxin peroxidase and trypanothione reductase, working in concert with the substrates NADPH and trypanothione. Here, we report the cloning and characterisation of the tryparedoxin (TryX) and tryparedoxin peroxidase (TryP) genes from C. fasciculata. Both genes are multicopy and organized in distinct tandem arrays in the genome. TryX encodes a 16 kDa protein, which belongs to the thioredoxin superfamily, sharing the WCPPC motif, whereas TryP encodes a 21 kDa protein belonging to a new class of peroxidases called 2-Cys peroxidoxins. Both TryX and TryP were expressed in Escherichia coli and the purified recombinant proteins shown to utilise hydrogen peroxide in the presence of NADPH, trypanothione and trypanothione reductase, similar to the native proteins. TryX is rapidly reduced by trypanothione, but weakly by glutathionylspermidine, glutathione or ovothiol A. TryP shows a broad substrate specificity and can reduced hydrogen peroxide, t-butyl hydroperoxide and cumene hydroperoxide with equal efficiency.
Mol Biochem Parasitol 1998 Oct 30
PMID:Cloning, expression and reconstitution of the trypanothione-dependent peroxidase system of Crithidia fasciculata. 985 11

Leishmania spp. encounter damaging oxygen metabolites from endogenous metabolic processes as well as from exogenous sources, such as inside the gut of the sandfly vector and within host macrophages. The recently described peroxidoxin protein family form part of a novel pathway for metabolising hydrogen peroxide that, in trypanosomatids, links peroxide reduction to NADPH oxidation via trypanothione. Here we report the cloning and characterisation of the Leishmania major peroxidoxin gene, tryparedoxin peroxidase (TryP). TryP is a multi-copy gene arranged in a complex tandem array located on the size polymorphic homologues of chromosome 15. Northern analysis showed that TryP expresses a single 1.6 kb mRNA throughout promastigote development. TryP encodes a 22-kDa protein with two conserved cysteine-containing domains that defines it as a 2-Cys peroxidoxin. Purified recombinant TryP protein catabolised hydrogen peroxide in the presence of the tryparedoxin homologue from Crithidia fasciculata (Cf-TryX), trypanothione, trypanothione reductase and NADPH. The demonstration that L. major utilises a three-protein peroxidase system confirms that this is a mechanism of protection against oxidative damage in this parasite.
Mol Biochem Parasitol 1998 Oct 30
PMID:Identification and characterisation of a functional peroxidoxin from Leishmania major. 985 12

A cDNA (C2C-Prx) corresponding to a 2Cys-peroxiredoxin (2Cys-Prx) was isolated from a leaf cDNA library of Chinese cabbage. The predicted amino acid sequence of C2C-Prx has 2 conserved cysteines and several peptide domains present in most of the 2Cys-Prx subfamily members. It shows the highest sequence homology to the 2Cys-Prx enzymes of spinach (88%) and Arabidopsis (86%). Southern analysis using the cDNA insert of C2C-Prx revealed that it consists of a small multigene family in Chinese cabbage genome. RNA blot analysis showed that the gene was predominantly expressed in the leaf tissue of Chinese cabbage seedlings, but the mRNA was generally expressed in most tissues of mature plant, except roots. The expression of C2C-Prx was slightly induced by treatment with H2O2 (100 microM) or Fe3+/O2/DTT oxidation system, but not by ABA (50 microM) or GA3 (10 microM). The C2C-Prx is encoded as a preprotein of 273 amino acids containing a putative chloroplast-targeting signal of 65 amino acids at its N-terminus. The N-terminally truncated recombinant protein (deltaC2C-Prx) migrates as a dimer in a non-reducing SDS-polyacrylamide gel and as a monomer in a reducing condition. The deltaC2C-Prx shows no immuno cross-reactivity to antiserum of the yeast thiol-specific antioxidant protein, and vice versa. The deltaC2C-Prx prevents the inactivation of glutamine synthetase and the DNA cleavage in the metal-catalyzed oxidation system. In the yeast thioredoxin system containing thioredoxin reductase, thioredoxin, and NADPH, the deltaC2C-Prx exhibits peroxidase activity on H2O2.
Plant Mol Biol 1999 Jul
PMID:Molecular cloning, expression, and functional characterization of a 2Cys-peroxiredoxin in Chinese cabbage. 1048 17

The peroxiredoxin (Prx) protein is expressed widely in animal tissues and serves an antioxidant function associated with removal of cellular peroxides. We have cloned two Prx genes and observed differential expression of Prx-I and Prx-II (formerly NKEF-A and NKEF-B) in purified rat brain cell cultures (Sarafian et al. [1998] Mol. Chem. Neuropathol. 34:39-51). We have examined regional and cell-type-specific expression of Prx-I and Prx-II in paraffin sections of human brain using immunohistochemical methods. These studies revealed a clear segregation of expression of these two gene products in different brain cell types. In the cerebral cortex, cerebellum, basal ganglia, substantia nigra, and spinal cord, Prx-I was expressed primarily in astrocytes, while Prx-II was expressed exclusively in neurons. Prx-I was also prominently expressed in ependymal cells and subependymal matrix of substantia nigra and basal ganglia. Prx-II was not expressed at uniform density in all neurons. In general, small neurons such as cerebellar granule neurons displayed little or no staining, while large neurons, such as hippocampal pyramidal and Purkinje neurons were heavily stained. The absence of expression of Prx-I in neurons and the selective expression of Prx-II in large neurons suggest that these antioxidant enzymes serve distinct functional roles that may reflect the different functions and biochemical activities of these cell types. Restricted expression of these genes may also contribute to the selective vulnerability of these cells to a wide variety of neuropathologic conditions.
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PMID:Differential expression of peroxiredoxin subtypes in human brain cell types. 1049 9


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