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)

To develop monoclonal antibodies (MAbs) to react with normal prion protein (PrPC) and abnormal isoform of prion protein (PrPSc), PrPSc was isolated from brains of 263 K scrapie-infected hamsters and immunized to PrP knockout mice. We developed two hybridomas, 3F10 and 1C5 (IgG1), of which epitope mappings were screened by using glutathione S-transferase (GST) fusion proteins of recombinant hamster prion protein and suitable peptides. 3F10 showed a high affinity for hamster and mouse PrP and was demonstrated to recognize the residues 137-151. 1C5 recognizes the region 119-130 corresponding to the GXXXG motif, the glycine zipper region, conserved in all mammals. In the immunohistochemical analysis, the positive staining for PrPSc was observed in the extracellular compartment of scrapie-infected brains but not in the normal brains. However, in Western blot, these antibodies recognized both normal and abnormal prion proteins. These results suggested that the developed mouse MAbs are specific to prion protein and can recognize abnormal prion protein more effectively than normal prion protein in immunohistochemistry. Therefore, these antibodies could be utilized as a useful reagent for the analysis of biochemical, structural, and functional properties between PrPC and PrPSc.
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PMID:Generation of monoclonal antibody recognized by the GXXXG motif (glycine zipper) of prion protein. 1704 82

Microtubule-associated protein tau is considered to play roles in many neurodegenerative diseases including some transmissible spongiform encephalopathies. To address the possible molecular linkage of prion protein (PrP) and tau, a GST-fusion segment of human tau covering the three-repeat region and various PrP segments was used in the tests of GST pull-down and immunoprecipitation. We found tau protein interacted with various style prion proteins such as native prion protein (PrPc) or protease-resistant isoform (PrPSc). Co-localization signals of tau and PrP were found in the CHO cell tranfected with both PrP and tau gene. The domain of interaction with tau was located at N-terminal of PrP (residues 23 to 91). The evidence of molecular interactions between PrP and tau protein highlights a potential role of tau in the biological function of PrP and the pathogenesis of TSEs.
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PMID:Study on interaction between microtubule associated protein tau and prion protein. 1717 55

The most essential and crucial step during the pathogenesis of transmissible spongiform encephalopathy is the conformational change of cellular prion protein to pathologic isoform. Casein kinase II (CK2) is a ubiquitously expressed and evolutionarily conserved pleiotropic protein kinase that is essential for viability. To explore the possible molecular interaction between CK2 and prion protein (PrP), the full-length sequences of human CK2alpha and CK2beta complementary DNA were amplified with reverse transcription-polymerase chain reaction using the total messenger RNA from cell line SH-SY5Y as the template; then, the fusion proteins histidine-CK2alpha and glutathione S-transferase-histidine-CK2beta were expressed in Escherichia coli. The interaction between CK2 and PrP was evaluated with co-immunoprecipitation and pull-down assays. The results demonstrated that recombinant PrP bound specifically with CK2alpha, but not with CK2beta. The native CK2 and PrP in hamster brains interacted with each other, forming protein complexes. Three different glycosylated forms of PrP (diglycosylated, monoglycosylated and unglycosylated PrP) from normal brains interacted with the CK2alpha subunit, though the unglycosylated PrP seemed to have a stronger binding ability with CK2alpha subunit. The domain responsible for interacting with CK2alpha was located at the C-terminal segment of PrP (residues 91-231). This study proposed reliable experimental data for the molecular interaction between PrP and CK2alpha (both in recombinant and native categories), scientific clues for further assessing the potential biological significance of the PrP-CK2 interaction, and the possible role of CK2 in the pathogenesis of prion diseases.
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PMID:Casein kinase II interacts with prion protein in vitro and forms complex with native prion protein in vivo. 1908 2

Previous studies have demonstrated that N,N-diethyldithiocarbamate (DEDC) elevates copper and promotes oxidative stress within the nervous system. However, whether these effects resolve following cessation of exposure or have the potential to persist and result in cumulative injury has not been determined. In this study, an established model for DEDC myelin injury in the rat was used to determine whether copper levels, oxidative stress, and neuromuscular deficits resolve following the cessation of DEDC exposure. Rats were exposed to DEDC for 8 weeks and then either euthanized or maintained for 2, 6 or 12 weeks after cessation of exposure. At each time point copper levels were measured by inductively coupled mass spectrometry to assess the ability of sciatic nerve, brain, spinal cord and liver to eliminate excess copper post-exposure. The protein expression levels of glutathione transferase alpha, heme oxygenase 1 and superoxide dismutase 1 in peripheral nerve and brain were also determined by western blot to assess levels of oxidative stress as a function of post-exposure duration. As an initial assessment of the bioavailability of the excess copper in brain the protein expression levels of copper chaperone for superoxide dismutase 1, and prion protein were determined by western blot as a function of exposure and post-exposure duration. Neuromuscular function in peripheral nerve was evaluated using grip strengths, nerve conduction velocities, and morphologic changes at the light microscope level. The data demonstrated that in peripheral nerve, copper levels and oxidative stress return to control levels within several weeks after cessation of exposure. Neuromuscular function also showed a trend towards pre-exposure values, although the resolution of myelin lesions was more delayed. In contrast, total copper and antioxidant enzyme levels remained significantly elevated in brain for longer post-exposure periods. The persistence of effects observed in brain suggests that the central nervous system is more susceptible to long-term cumulative adverse effects from dithiocarbamates. Additionally, significant changes in expression levels of chaperone for superoxide dismutase 1, and prion protein were observed consistent with at least a portion of the excess copper being bioactive.
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PMID:Peripheral nerve and brain differ in their capacity to resolve N,N-diethyldithiocarbamate-mediated elevations in copper and oxidative injury. 2045 88


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