Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whey acidic protein (WAP) has been measured by radioimmunoassay in the mammary gland of rats over pregnancy and lactation, and in mammary gland explants incubated with glucocorticoid or progestin in vitro. The radioimmunoassay used a novel fusion protein, glutathione transferase-WAP (GT-WAP), which can be iodinated with ease, unlike the native protein. Mammary gland WAP levels were low (less than 100 ng/mg tissue) until 2-3 days before parturition, but rose to 3 micrograms/mg tissue at day 21 of pregnancy. Immediately after parturition WAP content decreased to 1 micrograms/mg tissue, and then increased to greater than 5 micrograms/mg tissue during mid-lactation. Similarly, alpha-lactalbumin content was low throughout pregnancy (less than 10 ng/mg tissue) until day 20. Thereafter, values rose on the last day of pregnancy and the first day of lactation, fell briefly in early lactation like WAP, and rose to plateau levels by day 11 of lactation. In vitro explants prepared from mid-pregnant rats (day 14) synthesized WAP in the presence of insulin and prolactin. The synthetic glucocorticoid RU26988 (11 beta,17 beta-hydroxy-17 alpha-(1-propynyl)-androsta-1,4,6-trien-3-one) progressively increased WAP production to a maximum of greater than 10-fold basal (in the presence of insulin and prolactin) at 300 nM, in contrast with alpha-lactalbumin which showed a biphasic dose-response curve in explants from mid-pregnant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mammary gland whey acidic protein: ontogeny and changing patterns of steroid sensitivity. 269 56

In an effort to determine the role that metabolism by the cytochrome P-450 system plays in the development of hexachlorobenzene (HCB)-induced porphyria, Japanese quail were pretreated with either beta-naphthoflavone (BNF) or phenobarbital (PB) and then treated with HCB. PB or BNF pretreatment appeared to have no effect on the response of quail hepatic enzymes to HCB. There were no differences between the two groups in either the content of cytochrome P-450 or the activities of NADPH-cytochrome c reductase, glutathione transferase (microsomal or cytosolic), ethoxycoumarin-O-deethylase or ethoxyresorufin-O-deethylase following HCB treatment. These pretreatments did, however, markedly influence the development of porphyria in quail. BNF-treated birds had higher delta-aminolevulinic acid-synthetase (ALA-S) activities and developed porphyria much more rapidly than birds treated with HCB alone. Birds pretreated with PB did not exhibit porphyria even following 10 days of HCB. Although the ALA-S activities in this group were elevated slightly following HCB, they were about one-half of those seen in the BNF-pretreated HCB-treated group. These results may reflect a difference between the PB and BNF groups in the production of a porphyrogenic metabolite of HCB.
 ...
PMID:Hexachlorobenzene-induced porphyria in Japanese quail. Effect of pretreatment with phenobarbital or beta-naphthoflavone. 643 14

The porphyrinogenic action of 1,2,4-trichlorobenzene (TCB) was examined in 17-day-old embryos, day-old chicks, 18-day-old chickens and adult Japanese quail. The quail was found to be the most sensitive species towards TCB induced porphyria whereas the chick embryo was totally non-responsive. The liver porphyrins of Japanese quail were increased in a dose-dependent manner 1 day after TCB. Elevation in porphyrin levels in quail was associated with comparable increases in delta-aminolevulinic acid synthetase (ALA-S) activity 1 day after TCB treatment. In contrast, ferrochelatase activity was found to be unchanged 1 day after TCB. Multiple administration of TCB produced only a slight increase in liver porphyrin levels and ALA-S activity in quail. However, there was a marked induction in ferrochelatase activity suggesting increased porphyrin turnover. Liver glutathione and glutathione S-transferase activity were also significantly increased following repeated administration of TCB in quail, which could indicate an enhancement of detoxication of reactive metabolites of TCB. Thus, it is suggested that the inability of low multiple doses of TCB to cause porphyria in Japanese quail may be related to the low responsiveness of ALA-S but high inducibility of ferrochelatase liver GSH and glutathione S-transferase.
 ...
PMID:Studies on the porphyrinogenic action of 1,2,4-trichlorobenzene in birds. 663 2

Using part of the dnaK gene from Bacillus subtilis as a probe, a 4. 4-kbp SacI-BglII fragment of chromosomal DNA of Bacillus brevis, a protein-hypersecreting bacterium, was cloned. Nucleotide sequencing revealed 3 open reading frames in the order of grpE-dnaK-dnaJ homologues. We purified DnaK protein to homogeneity from B. brevis HPD31 harboring a multi-copy dnaK expression plasmid. Purified DnaK showed ATPase activity which was synergistically stimulated 14-fold by the addition of glutathione S-transferase-DnaJ and glutathione S-transferase-GrpE fusion proteins. DnaK hydrolyzed not only ATP but also CTP, UTP, and GTP at about 40% of the efficiency of ATP. The specific activity of DnaK-ATPase was 7.25x10-3 unit/mg protein (the turnover number against ATP was 0.47 min-1) under our assay conditions. The DnaK dimers dissociated into monomers on addition of ATP, GTP, CTP, UTP and ATPgammaS, but not ADP or AMP. DnaK formed a stable complex with permanently unfolded carboxymethylated alpha-lactalbumin but not with native alpha-lactalbumin, and this complex was dissociated by addition of ATP/Mg. Formation of this complex was inhibited in the presence of inorganic phosphate.
 ...
PMID:Molecular cloning of the dnaK locus, and purification and characterization of a DnaK protein from Bacillus brevis HPD31. 974 7

Clusterin is a highly conserved protein which is expressed at increased levels by many cell types in response to a broad variety of stress conditions. A genuine physiological function for clusterin has not yet been established. The results presented here demonstrate for the first time that clusterin has chaperone-like activity. At physiological concentrations, clusterin potently protected glutathione S-transferase and catalase from heat-induced precipitation and alpha-lactalbumin and bovine serum albumin from precipitation induced by reduction with dithiothreitol. Enzyme-linked immunosorbent assay data showed that clusterin bound preferentially to heat-stressed glutathione S-transferase and to dithiothreitol-treated bovine serum albumin and alpha-lactalbumin. Size exclusion chromatography and SDS-polyacrylamide gel electrophoresis analyses showed that clusterin formed high molecular weight complexes (HMW) with all four proteins tested. Small heat shock proteins (sHSP) also act in this way to prevent protein precipitation and protect cells from heat and other stresses. The stoichiometric subunit molar ratios of clusterin:stressed protein during formation of HMW complexes (which for the four proteins tested ranged from 1.0:1.3 to 1.0:11) is less than the reported ratios for sHSP-mediated formation of HMW complexes (1.0:1.0 or greater), indicating that clusterin is a very efficient chaperone. Our results suggest that clusterin may play a sHSP-like role in cytoprotection.
 ...
PMID:Clusterin has chaperone-like activity similar to that of small heat shock proteins. 1006 40

During tetrapyrrole biosynthesis the metalloenzyme porphobilinogen synthase (PBGS) catalyzes the condensation of two molecules of 5-aminolevulinic acid to form the pyrrole porphobilinogen. Pseudomonas aeruginosa PBGS was synthesized in Escherichia coli, and the enzyme was purified as a fusion protein with glutathione S-transferase (GST). After removal of GST, a molecular mass of 280 000 +/- 10 000 with a Stokes radius of 57 A was determined for native PBGS, indicating a homooctameric structure of the enzyme. Mg2+ stabilized the oligomeric state but was not essential for octamer formation. Alteration of N-terminal amino acids changed the oligomeric state and reduced the activity of the enzyme, revealing the importance of this region for oligomerization and activity. EDTA treatment severely inhibited enzymatic activity which could be completely restored by the addition of Mg2+ or Mn2+. At concentrations in the micromolar range Co2+, Zn2+, and Ni2+ partially restored EDTA-inhibited enzymatic activity while higher concentrations of Zn2+ inhibited the enzyme. Pb2+, Cd2+, and Hg2+ did not restore activity. A stimulatory effect of monovalent ions was observed. A Km of 0.33 mM for ALA and a maximal specific activity of 60 micromol h-1 mg-1 at the pH optimum of 8.6 in the presence of Mg2+ and K+ were found. pH-dependent kinetic studies were combined with protein modifications to determine the structural basis of two observed pKa values of approximately 7.9 (pKa1) and 9.5 (pKa2). These are postulated respectively as ionization of an active site lysine residue and of free substrate during catalysis. Some PBGS inhibitors were characterized. Finally, we succeeded in obtaining well-ordered crystals of P. aeruginosa PBGS complexed with the substrate analogue levulinic acid.
 ...
PMID:Production, purification, and characterization of a Mg2+-responsive porphobilinogen synthase from Pseudomonas aeruginosa. 1052 43

Alpha-synuclein, a major constituent of Lewy bodies (LBs) in Parkinson's disease (PD), has been implicated to play a critical role in synaptic events, such as neuronal plasticity during development, learning, and degeneration under pathological conditions, although the physiological function of alpha-synuclein has not yet been established. We here present biochemical evidence that recombinant alpha-synuclein has a chaperone-like function against thermal and chemical stress in vitro. In our experiments, alpha-synuclein protected glutathione S-transferase (GST) and aldolase from heat-induced precipitation, and alpha-lactalbumin and bovine serum albumin from dithiothreitol (DTT)-induced precipitation like other molecular chaperones. Moreover, preheating of alpha-synuclein, which is believed to reorganize the molecular surface of alpha-synuclein, increased the chaperone-like activity. Interestingly, in organic solvents, which promotes the formation of secondary structure, alpha-synuclein aggregated more easily than in its native condition, which eventually might abrogate the chaperone-like function of the protein. In addition, alpha-synuclein was also rapidly and significantly precipitated by heat in the presence of Zn2+ in vitro, whereas it was not affected by the presence of Ca2+ or Mg2+. Circular dichroism spectra confirmed that alpha-synuclein underwent conformational change in the presence of Zn2+. Taken together, our data suggest that alpha-synuclein could act as a molecular chaperone, and that the conformational change of the alpha-synuclein could explain the aggregation kinetics of alpha-synuclein, which may be related to the abolishment of the chaperonic-like activity.
 ...
PMID:Structural changes in alpha-synuclein affect its chaperone-like activity in vitro. 1120 70

A new kind of affinity electrophoresis called antibody affinity electrophoresis is a technique used to capture protein antigens based on their interactions with specific monoclonal or polyclonal antibodies incorporated in the polyacrylamide gel. Polyclonal anti-glutathione-S-transferase (anti-GST), monoclonal anti-bovine serum albumin (anti-BSA), and polyclonal anti-human alpha-lactalbumin are embedded in distinct areas of a 7.5% native polyacrylamide gel. Some of the embedded antibodies get covalently and/or noncovalently incorporated into the gel matrix network. Under electrophoresis conditions, these antibodies do not show significant electrophoretic mobility, as compared to their specific protein antigen analytes. We observed that electrophoretic migration of GST, BSA, and protein G ceases when they encounter anti-GST, anti-BSA, and immunoglobulin G, respectively.
 ...
PMID:Catching protein antigens by antibody affinity electrophoresis. 1549 Apr 55

Changes in erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) have been reported after exposure to different pesticides, including organophosphates and paraquat. In this study, we have determined ALA-D in 135 pesticide applicators (sprayers) from an intensive agriculture setting at two periods with different pesticide exposure. Acetylcholinesterase (AChE) was used as a reference biomarker. The effects of the combined polymorphism of enzymes involved in the detoxification of pesticides (paraoxonase (PON1), benzoylcholinesterase (BChE), and glutathione S-transferase (GSTM1 and GSTT1)) on the level of the target erythrocyte enzymes were also studied as biomarkers of individual susceptibility. Sprayers presented significant lower levels of ALA-D and AChE than controls (41.3% and 14.5%, respectively) at the high exposure period. When all biomarkers of individual susceptibility to pesticides were considered at the same time, the GSTT1 null allele determined higher ALA-D and AChE activities at the period of high exposure to pesticides. PON1 R allele in turn determined lower AChE activity at the low exposure period. Null genotype for both GST subclasses (GSTM1 and GSTT1) was found to be the unique independent predictor of pesticide-related symptomatology. Interestingly, sprayers were consistently underrepresented among carriers of "unfavourable" BChE variants. In conclusion, ALA-D appears to be an important biological indicator of pesticide exposure and PON1 and GSTT1 are relevant determinants of susceptibility to chronic pesticide poisoning.
 ...
PMID:Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility. 1592 24

In this study we evaluated the effect of diphenyl diselenide (PhSe)(2) on glycerol-induced acute renal failure in rats. Rats were pre-treated by gavage every day with (PhSe)(2 )(7.14 mg kg(-1)) for 7 days. On the eighth day, rats received an intramuscular injection of glycerol (8 mL kg(-1)). Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), delta-aminolevulinate dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities and ascorbic acid levels were evaluated in renal homogenates. Histopathological evaluations were also performed. The results demonstrated that (PhSe)(2) was able to protect against the increase in urea and creatinine levels and histological alterations in kidney induced by glycerol. (PhSe)(2) protected against the inhibition in delta-ALA-D, CAT and GPx activities and the reduction in ascorbic acid levels induced by glycerol in kidneys of rats. In conclusion, the present results indicate that (PhSe)(2) was effective in protecting against acute renal failure induced by glycerol.
 ...
PMID:Diphenyl diselenide protects against glycerol-induced renal damage in rats. 1948 1


1 2 3 Next >>