In vivo antigenotoxic effects of dietary agents and beverages co-administered with urethane: assessment of the role of glutathione S-transferase activity

Age of patients and brain oxidative stress may contribute to pathogenesis of Alzheimer's disease (AD). Erythrocytes (red blood cells, RBC) are considered as passive “reporter cells” for the oxidative status of the whole organism and are not well studied in AD. The aim of this work was to assess whether the antioxidant status of RBC changes in aging and AD. Blood was taken from AD and non-Alzheimer's dementia patients, aged-matched and younger controls. In vivo antioxidant status was assessed in each of the study subjects by measuring RBC levels of Н О , organic hydroperoxides, glutathione (GSH) and glutathione disulfide (GSSG), activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, and glucose-6-phosphate dehydrogenase. In both aging and dementia, oxidative stress in RBC was shown to increase and to be expressed in elevated concentrations of H O and organic hydroperoxides, decreased the GSH/GSSG ratio and glutathione S-transferase activity. Decreased glutathione peroxidase activity in RBC may be considered as a new peripheral marker for Alzheimer’s disease while alterations of other parameters of oxidative stress reflect age-related events.

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Overexpression of a directed mutant of 14-3-3ω in Arabidopsis leaves affects phosphorylation and protein content of nitrate reductaseThis paper is one of a selection published in a Special Issue comprising papers presented at the 50th Annual Meeting of the Canadian Society of Plant Physiologists (CSPP) held at the University of Ottawa, Ontario, in June 2008.

Botany ◽

10.1139/b09-003 ◽

2009 ◽

Vol 87 (7) ◽

pp. 691-701 ◽

Cited By ~ 2

Author(s):

Man-Ho Oh ◽

Joan L. Huber ◽

Wei Shen ◽

Gurdeep S. Athwal ◽

Xia Wu ◽

...

Keyword(s):

Defense Responses ◽

Cellular Proteins ◽

Signaling Proteins ◽

Glutathione S Transferase ◽

Independent Manner ◽

Client Proteins ◽

The University

The 14-3-3 family of proteins are highly conserved signaling proteins in eukaryotes that bind to their client proteins, usually through specific phosphorylated target sequences. While the 14-3-3 proteins are thought to interact with a wide array of cellular proteins, there have been few studies addressing the in-vivo role of 14-3-3. As one approach to study this in-vivo role, we generated transgenic Arabidopsis plants constitutively overexpressing a directed mutant of 14-3-3 isoform ω that inhibits phosphorylated nitrate reductase (pNR) in a largely divalent-cation-independent manner in vitro. The transgenic plants had increased relative phosphorylation of NR at the regulatory Ser-534 site and decreased NR activity measured in the presence of 5 mmol·L–1 MgCl2 relative to nontransgenic plants. In addition, total NR protein was increased and the protein half-life was increased about two-fold. Two-dimensional difference gel electrophoresis analysis of proteins extracted from leaves of plants expressing the mutant 14-3-3 identified numerous cellular proteins that were altered in abundance. In particular, several β-glucosidase and glutathione S-transferase isoforms were decreased in abundance relative to wild type plants suggesting a possible alteration in stress or defense responses.

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Functional Characterization of Membrane Sialyltransferase Activity of Human Platelets

10.1055/s-0039-1680349 ◽

1977 ◽

Author(s):

K. K. Wu ◽

C. Ku ◽

C. Smith

Keyword(s):

Enzyme Activity ◽

Functional Characterization ◽

Adenosine Diphosphate ◽

Normal Subjects ◽

Inhibitory Effect ◽

Human Platelets ◽

Transferase Activity ◽

Platelet Surface

To evaluate the role of membrane sialyltransferase in the initiation of platelet aggregation, we studied the stimulatory effect of epinephrine and adenosine diphosphate and the inhibitory effect of aspirin on the platelet surface sialyl transferase activity. The enzyme activity was assayed under optimal conditions as determined previously. The assay mixture consisted of intact washed human platelets, CMP-14C-sialic acid, desialated fetuin, Mn2+ and buffer to a final volume of 1 ml. The enzyme activity was enhanced to 172% of control by 1μH, 152% by 5μM and 146% by 10μM epinephrine. Adenosine diphosphate enhanced the enzyme activity to a lesser extent:103% at 1μM and 113% at 5μM. In contrast, aspirin inhibited the enzyme activity to 46% of control when 10μg/ml of aspirin was used. Higher concentrations of aspirin failed to cause further inhibition. In the in-vivo experiment, 600 mg aspirin was given to normal subjects and the surface enzyme activity was determined 12 hours later. The enzyme activity reduced to 43% following aspirin administration. Furthermore, we studied the enzyme activity in a patient with “aspirin-like” release disorder. While the mean surface enzyme activity of 10 normal subjects was 1.56 + 0.21 (S. D.) pmole-hr-1 per 108 platelets, the enzyme activity of the patient was only 0.91 pmole.hr-l. The results strongly suggest that the membrane sialyltransferase plays an important part in the initiation of platelet release reaction.

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Investigation of the effects of cephalosporin antibiotics on glutathione S-transferase activity in different tissues of rats in vivo conditions in order to drug development research

Drug and Chemical Toxicology ◽

10.1080/01480545.2018.1497644 ◽

2018 ◽

Vol 43 (4) ◽

pp. 423-428 ◽

Cited By ~ 8

Author(s):

Fikret Türkan ◽

Zübeyir Huyut ◽

Parham Taslimi ◽

Mehmet Tahir Huyut ◽

İlhami Gülçin

Keyword(s):

Drug Development ◽

Transferase Activity ◽

Development Research ◽

Glutathione S Transferase ◽

Cephalosporin Antibiotics ◽

Drug Development Research ◽

Different Tissues

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Possible role of blood insulin levels on glutathione S-transferase activities from different tissues of male rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-027 ◽

1990 ◽

Vol 68 (2) ◽

pp. 170-173 ◽

Cited By ~ 3

Author(s):

Cristina E. Carnovale ◽

Juan A. Monti ◽

Viviana A. Catania ◽

Maria C. Carrillo

Keyword(s):

Diabetic Rats ◽

Male Rats ◽

Blood Levels ◽

Transferase Activity ◽

Glutathione S Transferase ◽

Insulin Levels ◽

Blood Insulin ◽

Glucose Levels

The activity of in vitro glutathione S-transferase towards 1-chloro-2,4-dinitrobenzene was examined in liver, renal cortex, and small intestine (duodenum, jejunum, ileum) after the in vivo treatment of male Wistar rats with streptozotocin or alloxan. The studies were performed at 2, 10, 24, and 48 h and 7 and 15 days after streptozotocin treatment or 24 and 48 h after alloxan treatment. The results indicated that while the blood levels of insulin–glucose did not show variations, there were no alterations of the glutathione S-transferase activity in the tissues tested. On the other hand, when the treatments caused modifications on blood insulin–glucose levels, there were changes of glutathione S-transferase activity in all tissues (except in the ileum) in such a way that a direct relationship between plasma insulin levels and glutathione S-transferase activity could be demonstrated. These results were also confirmed through insulin administration to control and diabetic rats. The data demonstrate a possible regulation of glutathione S-transferase activity by blood insulin and (or) glucose levels in the tissues tested.Key words: insulin, glutathione S-transferase, streptozotocin, alloxan.

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Comparison of renal and hepatic glutathione S-transferases in the rat

Biochemical Journal ◽

10.1042/bj1580243 ◽

1976 ◽

Vol 158 (2) ◽

pp. 243-248 ◽

Cited By ~ 24

Author(s):

N Kaplowitz ◽

G Clifton ◽

J Kuhlenkamp ◽

J D Wallin

Keyword(s):

Organic Anion ◽

Gel Filtration ◽

Competitive Inhibitor ◽

Transferase Activity ◽

Close Correspondence ◽

Glutathione S Transferase ◽

Competitive Inhibitors ◽

Liver And Kidney ◽

Glutathione S Transferases

Renal and hepatic GSH (reduced glutathione) S-transferase were compared with respect to substrate and inhibitory kinetics and hormonal influences in vivo. An example of each of five classes of substrates (aryl, aralkyl, epoxide, alkyl and alkene) was used. In the gel filtration of renal or hepatic cytosol, an identical elution volume was found for all the transferase activities. Close correspondence in Km values was found for aryl, epoxide- and alkyl-transferase activities, with only the aralkyl activity significantly lower in kidney. Probenecid and p-aminohippurate were competitive inhibitors of renal aryl-, aralkyl-, epoxide- and alkyl-transferase activities and inhibited renal alkene activity. Close correspondence in Ki values for inhibition by probenecid of these activities in kidney and liver was found. In addition, furosemide was a potent competitive inhibitor of renal alkyl-transferase activity. Hypophysectomy resulted in significant increases in aryl-, araklyl-, and expoxide-transferase activities in liver and kidney. The hypophysectomy-induced increases in renal aryl- and aralkyl-transferase activities (approx. 100%) were more than twofold greater than increases in hepatic activities (approx. 40%). Administration of thyroxine prevented the hypophysectomy-induced increase in aryltransferase activity in both kidney and liver. The renal GSH S-transferases, in view of similarities to the hepatic activities, may play a role as cytoplasmic organic-anion receptors, as previously proposed for the hepatic enzymes.

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Golgi-Localized, γ-Ear-Containing, Arf-Binding Protein Adaptors Mediate Insulin-Responsive Trafficking of Glucose Transporter 4 in 3T3-L1 Adipocytes

Molecular Endocrinology ◽

10.1210/me.2005-0032 ◽

2005 ◽

Vol 19 (8) ◽

pp. 2145-2153 ◽

Cited By ~ 41

Author(s):

Lin V. Li ◽

Konstantin V. Kandror

Keyword(s):

Glucose Transporter ◽

Adaptor Proteins ◽

Dominant Negative ◽

Glucose Transporter 4 ◽

Glutathione S Transferase ◽

Insulin Responsiveness ◽

Vhs Domain

Abstract Small glucose transporter 4 (Glut4)-containing vesicles represent the major insulin-responsive compartment in fat and skeletal muscle cells. The molecular mechanism of their biogenesis is not yet elucidated. Here, we studied the role of the newly discovered family of monomeric adaptor proteins, GGA (Golgi-localized, γ-ear-containing, Arf-binding proteins), in the formation of small Glut4 vesicles and acquisition of insulin responsiveness in 3T3-L1 adipocytes. In these cells, all three GGA isoforms are expressed throughout the differentiation process. In particular, GGA2 is primarily present in trans-Golgi network and endosomes where it demonstrates a significant colocalization with the recycling pool of Glut4. Using the techniques of immunoadsorption as well as glutathione-S-transferase pull-down assay we found that Glut4 vesicles (but not Glut4 per se) interact with GGA via the Vps-27, Hrs, and STAM (VHS) domain. Moreover, a dominant negative GGA mutant inhibits formation of Glut4 vesicles in vitro. To study a possible role of GGA in Glut4 traffic in the living cell, we stably expressed a dominant negative GGA mutant in 3T3-L1 adipocytes. Formation of small insulin-responsive Glut4-containing vesicles and insulin-stimulated glucose uptake in these cells were markedly impaired. Thus, GGA adaptors participate in the formation of the insulin-responsive vesicular compartment from the intracellular donor membranes both in vivo and in vitro.

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