A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7)
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2.
Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of glutathione from gamma-glutamylcysteine and glycine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.3.
A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.
A covalently linked dimeric nonessential amino acid formed by the oxidation of CYSTEINE. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
A cyclized derivative of L-GLUTAMIC ACID. Elevated blood levels may be associated with problems of GLUTAMINE or GLUTATHIONE metabolism.
Catalyzes the oxidation of GLUTATHIONE to GLUTATHIONE DISULFIDE in the presence of NADP+. Deficiency in the enzyme is associated with HEMOLYTIC ANEMIA. Formerly listed as EC 1.6.4.2.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
A sulfhydryl reagent which oxidizes sulfhydryl groups to the disulfide form. It is a radiation-sensitizing agent of anoxic bacterial and mammalian cells.
An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.
Compounds containing the -SH radical.
Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9.
The action of a drug in promoting or enhancing the effectiveness of another drug.
Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION).
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Inorganic or organic compounds that contain arsenic.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
An enzyme that catalyzes the conversion of ATP, L-glutamate, and NH3 to ADP, orthophosphate, and L-glutamine. It also acts more slowly on 4-methylene-L-glutamate. (From Enzyme Nomenclature, 1992) EC 6.3.1.2.
Antimetabolites that are useful in cancer chemotherapy.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.
A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.
A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.
A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.
A plant genus of the family Passifloraceae, order Violales, subclass Dilleniidae, class Magnoliopsida. They are vines with ornamental flowers and edible fruit.
Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)
The study of natural phenomena by observation, measurement, and experimentation.
Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)
The study of the structure, behavior, growth, reproduction, and pathology of cells; and the function and chemistry of cellular components.
Ordered compilations of item descriptions and sufficient information to afford access to them.
Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines.
Increase in constituent cells in the PROSTATE, leading to enlargement of the organ (hypertrophy) and adverse impact on the lower urinary tract function. This can be caused by increased rate of cell proliferation, reduced rate of cell death, or both.
Nitrogenous products of NITRIC OXIDE synthases, ranging from NITRIC OXIDE to NITRATES. These reactive nitrogen intermediates also include the inorganic PEROXYNITROUS ACID and the organic S-NITROSOTHIOLS.
The application of electronic, computerized control systems to mechanical devices designed to perform human functions. Formerly restricted to industry, but nowadays applied to artificial organs controlled by bionic (bioelectronic) devices, like automated insulin pumps and other prostheses.
Exclusive legal rights or privileges applied to inventions, plants, etc.
An orally active synthetic progestational hormone used often in combinations as an oral contraceptive.

Influence of glutathione levels and heat-shock on the steady-state levels of oxidative DNA base modifications in mammalian cells. (1/573)

The effects of thiols, ascorbic acid and thermal stress on the basal (steady-state) levels of oxidative DNA base modifications were studied. In various types of untreated cultured mammalian cells, the levels of total glutathione were found to be inversely correlated with the levels of DNA base modifications sensitive to the repair endonuclease Fpg protein, which include 8-hydroxyguanine (8-oxoG). A depletion of glutathione by treatment with buthionine sulphoximine increased the steady-state level in AS52 Chinese hamster cells by approximately 50%. However, additional thiols in the culture medium did not reduce the level of Fpg-sensitive base modifications: 0-10 mM N-acetylcysteine had no effect, whereas cysteine ethylester even increased the oxidative DNA damage at concentrations >0.1 mM. Similarly, ascorbic acid (0-20 mM) failed to reduce the steady-state levels. When AS52 cells were grown at elevated temperature (41 degrees C), the steady-state level of the oxidative DNA modifications increased by 40%, in spite of a concomitant 1.6-fold increase of the cellular level of total glutathione. Depletion of glutathione at 41 degrees C nearly doubled the already elevated level of oxidative damage. A constitutive expression of the heat-shock protein Hsp27 in L929 mouse fibrosarcoma cells at 37 degrees C increased the glutathione level by 60%, but had little effect on the level of oxidative DNA damage.  (+info)

Role of antioxidant defenses against ethanol-induced damage in cultured rat gastric epithelial cells. (2/573)

Reactive oxygen species appears to be involved in the pathogenesis of ethanol-induced gastric mucosal injury in vivo. Because ingested ethanol diffuses into the gastric mucosa, targeting both epithelium and endothelium, in the present study we examined the possible protective effect of antioxidants on ethanol damage in gastric epithelial cells and endothelial cells in vitro. Cytotoxicity by ethanol was quantified by measuring 51Cr release. The effects of impairment of the glutathione redox cycle and of inhibition of cellular catalase were examined. The generation of superoxide was assessed by the reduction in cytochrome c. Ethanol caused a time- and dose-dependent increase in 51Cr release from epithelial cells. Incubation of cells with DL-buthionine-(S,R)-sulfoximine, while reducing glutathione production, dose dependently enhanced ethanol-induced injury. 1,3-Bis(chloroethyl)-nitrosourea, while inhibiting glutathione reductase activity, also sensitized cells to ethanol. In contrast, the inhibition of catalase with 3-amino-1,2, 4-triazole did not alter the susceptibility of epithelial cells to ethanol. Ethanol induced damage to endothelial cells in a similar fashion. In endothelial cells, however, neither impairment of the glutathione cycle nor inhibition of catalase influenced ethanol-induced damage. Epithelial cells, when exposed to ethanol, increased superoxide production as a function of ethanol concentration, whereas endothelial cells did not. The glutathione redox cycle, but not cellular catalase, plays a critical role in protecting epithelial cells against ethanol damage, whereas neither antioxidant seems to play a role in protection of endothelial cells. The distinct difference in antioxidant protection against ethanol appears to depend on the capability of each cell to produce cytotoxic oxygen species in response to ethanol exposure.  (+info)

Involvement of N-acetylcysteine-sensitive pathways in ricin-induced apoptotic cell death in U937 cells. (3/573)

We have found that the antioxidant N-acetylcysteine (NAC) strongly inhibited ricin-induced apoptotic cell death in U937 cells (human myeloid leukemia), as judged by cytotoxicity, nuclear morphological change, and DNA fragmentation. Consistent with these observations, a significant depletion of cellular glutathione was observed in ricin-treated cells, and NAC prevented the decrease in cellular glutathione. On the other hand, among the caspase inhibitors tested, Z-Asp-CH2-DCB, which inhibited ricin cytotoxicity, also suppressed ricin-mediated glutathione depletion, while NAC did not affect the generation of caspase-3 like activity in ricin-treated cells. These results suggest that glutathione loss takes place downstream from caspase activation during the ricin-induced apoptotic process. Treatment with a specific inhibitor of glutathione biosynthesis, buthionine sulfoximine (BSO) failed to induce apoptosis, and had no effect on the overall extent of ricin-induced apoptosis, even though the glutathione level was decreased to less than 5% of the control level. However, NAC still protected against ricin-induced apoptosis in the BSO-treated cells. We conclude that glutathione loss is one of several apoptotic changes caused by ricin, but is not a sufficient factor for the progress of apoptosis. NAC may prevent ricin-induced apoptosis through maintaining an intracellular reducing condition by acting as a thiol supplier.  (+info)

Apoptosis in hematopoietic cells (FL5.12) caused by interleukin-3 withdrawal: relationship to caspase activity and the loss of glutathione. (4/573)

The mechanism of cell death caused by cytokine deprivation remains largely unknown. FL5.12 cells (a murine prolymphocytic cell line), following interleukin-3 (IL-3) withdrawal, undergo a decrease in intracellular glutathione (GSH) that precedes the onset of apoptosis. In the present study, the induction of apoptosis following IL-3 withdrawal or GSH depletion with DL-buthionine-[S,R,]-sulfoximine (BSO) was examined. Both conditions caused time-dependent increases in phosphatidylserine externalization, acridine orange and ethidium bromide staining, decreases in mitochondrial membrane potential, processing and activation of caspase-3 and proteolysis of the endogenous caspase substrate poly(adenosine diphosphate ribose)polymerase (PARP). Apoptosis induced by IL-3 deprivation but not BSO also caused lamin B1 cleavage, suggesting activation of caspase-6. Despite a more profound depletion of GSH after BSO than withdrawal of IL-3, the extent of apoptosis was somewhat lower. Benzyloxycarbonyl-Val-Ala-Asp(OMe)fluoromethyl ketone (z-VAD.fmk) blocked this caspase activity and prevented cell death after BSO exposure but not after IL-3 deprivation. Following IL-3 withdrawal, the caspase inhibitors z-VAD.fmk and boc-asp(OMe)fluoromethylketone (boc-asp.fmk) prevented the cleavage and activation of caspase-3, the breakdown of lamin B1 and partially mitigated PARP degradation. However, the externalization of phosphatidylserine, the fall in mitochondrial membrane potential and subsequent apoptotic cell death still occurred. These results suggest that IL-3 withdrawal may mediate cell death by a mechanism independent of both caspase activation and the accompanying loss of GSH.  (+info)

ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. (5/573)

Non-P-glycoprotein-mediated multidrug-resistant C-A120 cells that overexpressed multidrug resistance protein (MRP) were 10.8- and 29. 6-fold more resistant to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and SN-38, respectively, than parental KB-3-1 cells. To see whether MRP is involved in CPT-11 and SN-38 resistance, MRP cDNA was transfected into KB-3-1 cells. The transfectant, KB/MRP, which overexpressed MRP, was resistant to both CPT-11 and SN-38. 2-[4-Diphenylmethyl)-1-piperazinyl]ethyl-5-(trans-4,6-dimethyl-1,3 , 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) and MK571, which reversed drug resistance in MRP overexpressing multidrug-resistant cells, significantly increased the sensitivity of C-A120 and KB/MRP cells, but not of KB-3-1 cells, to CPT-11 and SN-38. The accumulation of both CPT-11 and SN-38 in C-A120 and KB/MRP cells was lower than that in KB-3-1 cells. The treatment with 10 microM PAK-104P increased the accumulation of CPT-11 and SN-38 in C-A120 and KB/MRP cells to a level similar to that found in KB-3-1 cells. The ATP-dependent efflux of CPT-11 and SN-38 from C-A120 and KB/MRP cells was inhibited by PAK-104P. DNA topoisomerase I expression, activity, and sensitivity to SN-38 were similar in the three cell lines. Furthermore, the conversion of CPT-11 to SN-38 in KB-3-1 and C-A120 cell lines was similar. These findings suggest that MRP transports CPT-11 and SN-38 and is involved in resistance to CPT-11 and SN-38 and that PAK-104P reverses the resistance to CPT-11 and SN-38 in tumors that overexpress MRP.  (+info)

Protection against hydrogen peroxide cytotoxicity in rat-1 fibroblasts provided by the oncoprotein Bcl-2: maintenance of calcium homoeostasis is secondary to the effect of Bcl-2 on cellular glutathione. (6/573)

The oncoprotein Bcl-2 protects cells against apoptosis, but the exact molecular mechanism that underlies this function has not yet been identified. Studying H2O2-induced cell injury in Rat-1 fibroblast cells, we observed that Bcl-2 had a protective effect against the increase in cytosolic calcium concentration and subsequent cell death. Furthermore, overexpression of Bcl-2 resulted in an alteration of cellular glutathione status: the total amount of cellular glutathione was increased by about 60% and the redox potential of the cellular glutathione pool was maintained in a more reduced state during H2O2 exposure compared with non-Bcl-2-expressing controls. In our cytotoxicity model, disruption of cellular glutathione homoeostasis closely correlated with the pathological elevation of cytosolic calcium concentration. Stabilization of the glutathione pool by Bcl-2, N-acetylcysteine or glucose delayed the cytosolic calcium increase and subsequent cell death, whereas depletion of glutathione by dl-buthionine-(S, R)-sulphoximine, sensitized Bcl-2-transfected cells towards cytosolic calcium increase and cell death. We therefore suggest that the protection exerted by Bcl-2 against H2O2-induced cytosolic calcium elevation and subsequent cell death is secondary to its effect on the cellular glutathione metabolism.  (+info)

Significance of glutathione-dependent antioxidant system in diabetes-induced embryonic malformations. (7/573)

Hyperglycemia-induced embryonic malformations may be due to an increase in radical formation and depletion of intracellular glutathione (GSH) in embryonic tissues. In the past, we have investigated the role of the glutathione-dependent antioxidant system and GSH on diabetes-related embryonic malformations. Embryos from streptozotocin-induced diabetic rats on gestational day 11 showed a significantly higher frequency of embryonic malformations (neural lesions 21.5 vs. 2.8%, P<0.001; nonneural lesions 47.4 vs. 6.4%, P<0.001) and growth retardation than those of normal mothers. The formation of intracellular reactive oxygen species (ROS), estimated by flow cytometry, was increased in isolated embryonic cells of diabetic rats on gestational day 11. The concentration of intracellular GSH in embryonic tissues of diabetic pregnant rats on day 11 was significantly lower than that of normal rats. The activity of y-glutamylcysteine synthetase (gamma-GCS), the rate-limiting GSH synthesizing enzyme, in embryos of diabetic rats was significantly low, associated with reduced expression of gamma-GCS mRNA. Administration of buthionine sulfoxamine (BSO), a specific inhibitor of gamma-GCS, to diabetic rats during the period of maximal teratogenic susceptibility (days 6-11 of gestation) reduced GSH by 46.7% and increased the frequency of neural lesions (62.1 vs. 21.5%, P<0.01) and nonneural lesions (79.3 vs. 47.4%, P<0.01). Administration of GSH ester to diabetic rats restored GSH concentration in the embryos and reduced the formation of ROS, leading to normalization of neural lesions (1.9 vs. 21.5%) and improvement in nonneural lesions (26.7 vs. 47.4%) and growth retardation. Administration of insulin in another group of pregnant rats during the same period resulted in complete normalization of neural lesions (4.3 vs. 21.5%), nonneural lesions (4.3 vs. 47.4%), and growth retardation with the restoration of GSH contents. Our results indicate that GSH depletion and impaired responsiveness of GSH-synthesizing enzyme to oxidative stress during organogenesis may have important roles in the development of embryonic malformations in diabetes.  (+info)

Molecular basis for hepatic detoxifying enzyme induction by 2-(allylthio)pyrazine in rats in comparison with oltipraz: effects on prooxidant production and DNA degradation. (8/573)

The expression of hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTs) by 2-(allylthio)pyrazine (2-AP), an experimental chemopreventive agent, was investigated in rats. Northern blot analysis revealed that 2-AP caused increases in mEH, rGSTA2/3/5, and rGSTM1/2 mRNA levels. mEH and rGSTA2 proteins were also induced. Molecular basis of the enzyme induction by 2-AP was studied in comparison with oltipraz (Olt). Rats exposed to buthionine sulfoximine, a GSH-depleting agent, before treatment with either 2-AP or Olt exhibited greater increases in the mRNA levels than the individual treatment. Conversely, increases of the mRNAs were prevented by cysteine treatment, indicating that metabolic intermediates or reactive oxygens produced from the agents could be reduced by cysteine. Gel shift analysis revealed that nuclear factor-kappaB, which is associated with the altered cellular redox state, was not activated by the agents. Effects of these agents on the breakage of phix-174 DNA were compared in vitro. 2-AP effectively reduced the conversion of supercoiled DNA to the open circular form induced by benzenetriol and prevented benzenetriol- and iron-catalyzed degradation of DNA, whereas Olt failed to prevent strand breakage of DNA. These results provided evidence that: 1) 2-AP was effective in elevating the hepatic mEH and GST gene expression in rats, which might be mediated with the production of reactive oxygen species; 2) nuclear factor-kappaB activation was not involved in the induction of the detoxifying enzymes by either 2-AP or Olt in spite of their production of reactive oxygens in vivo; and 3) the antioxidant effect of 2-AP in vitro differed from that of Olt.  (+info)

TY - JOUR. T1 - Effect of L-buthionine-(S,R)-sulphoximine, an inhibitor of γ-glutamylcysteine synthetase on peroxynitrite- and endotoxic shock-induced vascular failure. AU - Cuzzocrea, Salvatore. AU - Zingarelli, Basilia. AU - OConnor, Michael. AU - Salzman, Andrew L.. AU - Szabo, Csaba. PY - 1998. Y1 - 1998. N2 - 1. Peroxynitrite, a cytotoxic oxidant formed from the reaction of nitric oxide (NO) and superoxide is a mediator of cellular injury in ischaemia/reperfusion injury, shock and inflammation. Here we investigated whether L-buthionine-(S,R)-sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, alters endothelial and vascular smooth muscle injury in response to peroxynitrite in vitro and during endotoxic shock in vivo. 2. In human umbilical vein endothelial cells and in rat aortic smooth muscle cells, BSO (1 mM, for 24 h) enhanced, whereas glutathione (3 mM) or glutathione ethyl ester (3mM) attenuated the peroxynitrite (100-1000 μM)-induced suppression of mitochondrial ...
Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20(S)-camptothecin, SN-38 [7-ethyl-10-hydroxy-20(S)-camptothecin], topotecan, and 7-chloromethyl-10,11-methylenedioxy-20(S)camptothecin (CMMDC). The greatest potentiation was observed with the alkylating camptothecin CMMDC. Buthionine sulfoximine pretreatment also increased the number of camptothecin-induced DNA-protein crosslinks, indicating that GSH affects the mechanism of action of camptothecin.
The results of this study show that, in Sprague-Dawley rats, oxidative stress increased BP, which was associated with renal AT1R upregulation and exaggerated signaling. In BSO-treated rats, Ang II caused significantly higher NKA stimulation and failed to cause inhibition of NKA activity, as seen in control rats. Our data shows that AT1R-mediated NKA stimulation by low Ang II concentration involves MAP kinase, whereas the inhibition at high Ang II concentration involves NO-cGMP signaling. Interestingly, whereas picomolar concentration of Ang II showed robust stimulation of MAP kinase in BSO-treated rats, it failed to activate NO-cGMP signaling and inhibit NKA activity at micromolar concentrations. In control rats, Ang II stimulated NADPH oxidase, but the activation of this enzyme was much higher in BSO-treated rats. In addition, Ang II-mediated, AT1R-dependent O2•− production was also contributed by NOS in BSO-treated rats. Furthermore, Ang II-mediated Pyk2 stimulation was also higher in ...
The gastrointestinal tract is exposed to pro-oxidants from food, host immune factors, and microbial pathogens, which may induce oxidative damage. quercetin protection was explored in Caco2. Reversed H2O2-induced cell damage and decreased reactive oxygen species and apoptosis ratio were observed in quercetin-treated cells. Also, quercetin increased expression of the glutamate-cysteine Rocilinostat inhibitor database ligase catalytic subunit (GCLC), the first rate-limiting enzyme of glutathione synthesis, and increased intracellular GSH concentration under H2O2 treatment. This effect was abolished by the GCLC inhibitor buthionine sulfoximine. These results indicated that quercetin can improve cell proliferation and increase intracellular GSH concentrations by upregulating transcription of GCLC to get rid of excessive reactive air species (ROS). Elevated extracellular H2O2 focus induced by quercetin under oxidative tension was linked to the inhibition of AQP3 and upregulation of NOX1/2, which might ...
Cancer stem cells (CSCs) exhibit lower intracellular reactive oxygen species (ROS) levels than non-CSCs, which may be due to the increased expression of free radical scavenging systems. Exogenous agents may be useful to increase ROS and selectively kill CSCs by oxidative stress. Here we tested a combination approach to increase ROS as an effective strategy to eradicate breast CSCs and metastases. Buthionine sulfoximine (BSO) and auranofin (AU) were used to deplete glutathione (GSH) and inhibit thioredoxin reductase (TR), respectively, while mitochondrial-targeted decyltriphenylphosphonium (dTPP) was used to elevate ROS levels. In vitro clonogenicity assays using SUM159 cells showed that treatment with dTPP alone resulted in ,30% survival, while AU+BSO, BSO+dTPP and AU+BSO+dTPP all resulted in ,1% survival. These effects were reversible with N-acetylcysteine pre-treatment. The Aldefluor+ (CSC) population was also measured following drug treatment in vitro. dTPP or AU treatment alone resulted in ...
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L-BUTHIONINE (CAS 13073-21-7) Market Research Report 2018 aims at providing comprehensive data on l-buthionine market globally and regionally (Europe,
We investigated the toxicity of hemoglobin/myoglobin on endothelial cells under oxidative stress conditions that include cellular hypoxia and reduced antioxidant capacity. Bovine aorta endothelial cells (BAECs), grown on microcarrier beads, were subjected to cycles of hypoxia and reoxygenation in a small volume of medium, and endothelial cell monolayers were depleted of their intracellular glutathione (GSH) by treatment with buthionine sulfoximine. Incubation of diaspirin cross-linked hemoglobin (DBBF-Hb) or horse skeletal myoglobin (Mb) with BAECs subjected to 3 h of hypoxia caused transient oxidation of the hemoproteins to the ferryl form (Fe(4+)). Formation of the ferryl intermediate was decreased in a concentration-dependent manner by the addition of L-arginine, a substrate of NO synthase, after 3 h of hypoxia. Optimal inhibition of ferryl formation, possibly due to the antioxidant action of NO, was achieved with 900 microM L-arginine. Addition of hydrogen peroxide to GSH-depleted cells in the
A chlorambucil (CLB)-resistant cell line, N50-4, was developed from the established mouse fibroblast cell line NIH 3T3, by multistep drug selection. The mutant cells exhibited greater than 10-fold resistance to CLB. Alterations in GSH and glutathione S-transferase (GST) were found in CLB-resistant variants. A 7-10-fold increase in cellular GSH content and a 3-fold increase in GST activity were detected in N50-4 cells, compared with parental cells, as determined by enzymatic assays. An increase in steady state levels of the GST-alpha isozyme mRNA was found in the CLB-resistant cells, as analyzed by Northern blotting. No GST gene amplification or rearrangement was shown by Southern blot analysis. To test the relative roles of GSH and GST in CLB resistance, a number of GSH- and GST-blocking agents were used. The CLB toxicity was significantly enhanced in N50-4 cells by administration of either the GSH-depleting agent buthionine sulfoximine or the GST inhibitors ethacrynic acid or indomethacin. The ...
Stress and starvation increased liver metallothionein (MT) and decreased liver glutathione (GSH) levels. Serum cysteine plus cystine levels were increased by stress. The exogenous administration of GSH, while not modifying hepatic GSH content, increased liver MT levels in basal and starved rats but not in stressed rats. Liver and serum cysteine levels were increased by GSH administration, a process partially reverted by the irreversible inhibitor of gamma-glutamyl transpeptidase, alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid. Mouse and rat liver MT levels were also increased by buthionine sulfoximine, an inhibitor of GSH synthesis, indicating that GSH is not a necessary precursor of MT. In addition, the hepatic MT content was increased by the administration of cysteine in a dose-response manner. These results suggest that hepatic MT synthesis is elevated by increased cysteine pools, and that MT, GSH and cysteine levels are somehow inter-related. MT, besides GSH, may be contemplated as ...
Administration of cyclophosphamide at a dose which is lethal to 10% of control athymic nude mice resulted in sudden death within 3 h in all mice that had been pretreated with the glutathione synthesis inhibitor l-buthionine-SR-sulfoximine. In Fischer 344 rats pretreated with l-buthionine-SR-sulfoximine, the cyclophosphamide dose producing 100% acute toxicity was lowered from 500-150 mg/kg; cardiac monitoring revealed ventricular fibrillation to be the cause of death. These and additional studies reported demonstrate that cytoplasmic glutathione is an important protectant against the cardiac and skeletal muscle toxicity of cyclophosphamide and indicate that such toxicity may be substantially increased by glutathione depletion. Since diet and many drugs (including cyclophosphamide itself) are known to affect glutathione levels, the present studies suggest that cardiac and skeletal muscle glutathione content is likely to be a clinically significant determinant of the frequency and severity of the ...
Purpose:Cancer cells (relative to normal cells) demonstrate increased steady-state levels of hydroperoxides that are compensated for by increased glucose and hydroperoxide metabolism. The current study determined if inhibitors of glucose and hydroperoxide metabolism could induce chemo-radio-sensitization by enhancing oxidative stress in lung cancer cells. Experimental Design:A549 and NCI-H292 human lung carcinoma cells were treated with 2-Deoxy-D-glucose (2DG) combined with carboplatin (carbo) + ionizing radiation (IR). Lung cancer cells were further sensitized with inhibitors of glutathione- and thioredoxin-dependent metabolism [buthionine sulfoximine (BSO) and auranofin (Au), respectively] in vitro and in vivo. Results:When 2DG was combined with carbo+IR, clonogenic cell killing was enhanced in A549 and NCI-H292 cells and this combination was more effective than paclitaxel+carbo+IR. The thiol antioxidant (N-acetylcysteine, NAC) was capable of protecting cancer cells from 2DG+carbo-induced cell ...
ROS-inducing anticancer drugs such as buthionine sulphoximine, β-lapachone, imexon, and methoxyestradiol that directly target antioxidant pathways have been developed for clinical applications (94). Moreover, many clinically used drugs such as arsenic trioxide, taxol, paclitaxel, doxorubicin, and platinum-derived drugs also induce ROS and this contributes to their overall anticancer activity (rev. in ref. 94). Although ROS-inducing anticancer agents induce DNA damage and both oxidative and ER stress through initial mitochondrial damage, there are also reports that these compounds induce many of the same responses and genes observed after Sp knockdown (Fig. 1). Moreover, initial studies showed that pro-oxidants such as hydrogen peroxide, t-butyl hydroperoxide, pharmacologic doses of ascorbate (generates hydrogen peroxide), and arsenic trioxide downregulated Sp1, Sp3, Sp3, and Sp-regulated genes (71-73). Similar ROS inducers such as curcumin, BITC, HDAC inhibitors, celastrol, CDDO-Me, GT-094, ...
Have you ever heard of glutathione (pronounced; gloota-thigh-own)? Neither has almost anyone else. Many researchers say its probably the most important substance we require to stay healthy. Many go as far to say its the secret to prevent aging. So wheres Oprah, and the rest of the media? A quick search of the term glutathione on PubMed.gov reveals 94,117 scholarly articles, reviews and abstracts. Present in every cell of our body, glutathione levels just might be one of the best biochemical markers there is; the higher your glutathione levels are the healthier you will be. Glutathione deficiency is found in almost all patients with extreme illnesses, e.g., cancer, heart disease, Parkinsons disease, Alzheimers, arthritis, liver disease, diabetes and more. In fact, researchers are concluding glutathione deficiency may play a role in patients with schizophrenia. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione was observed ...
Routine cell line maintenance involves removal of waste products and replenishment of nutrients via replacement of cell culture media. Here, we report that routine maintenance of three discrete cell lines (HSB-CCRF-2 and Jurkat T cells, and phaeo-chromocytoma PC12 cells) decreases the principal cellular antioxidant, glutathione, by up to 42% in HSB-CCRF-2 cells between 60 and 120min after media replenishment. However, cellular glutathione levels returned to baseline within 5h after passage. The decrease in glutathione was associated with modulation of the response of Jurkat T cells to apoptotic and mitogenic signals. Methotrexate-induced apoptosis over 16h, measured as accumulation of apoptotic nucleoids, was decreased from 22 to 17% if cells were exposed to cytotoxic agent 30min after passage compared with cells exposed to MTX in the absence of passage. In contrast, interleukin-2 (IL-2) production over 24h in response to the toxin phytohaemagglutinin (PHA), was increased by 34% if cells were challenged
• Critical illness is associated with both immunosuppression and glutathione deficiency. We determined if in vivo depletion of glutathione would adversely affec
The term DEM, DTM and DSM has several meanings and are not always understood properly, correctly or misinterpreted. Difference between DEM/DTM and DSM
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CHRYSO®Dem Eco 2 - DPV jest gotowym do u?ycia ?rodkiem do opó?nionego rozformowywania (antyadhezyjnym), o sk?adzie czysto ro?linnym, a zatem bezpiecznym dla u?ytkowników ...
CHRYSO®Dem DPV Eco 2 jest gotowym do u?ycia ?rodkiem do opó?nionego rozformowywania (antyadhezyjnym), o sk?adzie czysto ro?linnym, a zatem bezpiecznym dla u?ytkowników ...
Die Universität zu Köln ist eine Exzellenzuniversität mit dem klassischen Fächerspektrum einer Volluniversität. Als eine der größen Hochschulen Europas arbeitet sie in Forschung und Lehre auch international auf höchstem Niveau.
In einem langwierigen Prozess entscheidet der Bundesgerichtshof zugunsten von Biofrontera. Das Gericht hebt ein Urteil des Oberlandesgerichts Köln aus dem
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توسعۀ ‌فیزیکی شهر کامیاران و چگونگی برخورد آن با واحدهای مختلف طبیعی و ژئومورفیک شامل تپه-ها، رودخانه، آبرفت-های قدیمی و خطوط گسل مسائل مهم و چالش برانگیزی را به همراه داشته است. پژوهش حاضر در پی شناخت عوامل موثر بر مکان‌گزینی و توسعه‌فیزیکی شهر و ارائه مدلی مناسب با توجه به این عوامل جهت توسعه آتی شهر کامیاران می-باشد. این پژوهش از نظر هدف کاربردی و از نظر روش، توصیفی - تحلیلی است. در این بررسی از مشاهدۀ میدانی، عکس‌های‌هوایی، تصاویر ماهواره‌ای (لندست) و DEM27 متر منطقه، جهت استخراج بخش عمده‌ای از اطلاعات و نقشه‌ها در محیط GISاستفاده شده است. مجموعه داده-ها
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DEM and RSI: 此 DEM 和 RSI 指标基于两个流行指标 - DeMarker + RSI。它的工作像一个半自动交易系统,识别超卖和超买级别,给出对应的开仓信号。 交易建议: 在任意货币对的任意时间帧图表上挂载指标 (它在 EURUSD M1 图表上显示最佳)。 当此时有买/卖信号 - 中文
Kräuterzubereitung Unser doppelt fermentierter schwarzer Knoblauch enthält die wichtige Verbindung S-Allycystein mit dem
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The trapping mechanisms of the PET hypoxia imaging agent copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu(ATSM)) remain unresolved, although its reduction prior to dissociation may be mediated by intracellular thiols. Glutathione (GSH) is the most abundant intracellular thiol, and its redox status changes in cancer cells and ischaemic myocardium (two prime applications for 64Cu(ATSM) PET). We therefore investigated whether modification of intracellular GSH content affects the hypoxia selectivity of 64Cu(ATSM). Isolated rat hearts (n = five per group) were perfused with aerobic buffer (equilibrated with 95%O2/5%CO2) for 15 min, then hypoxic buffer (95%N2/5%CO2) for 20 min. Cardiac glutathione was depleted by buthionine sulphoximine (BSO, 4 mmol/kg/ 48 h intraperitoneal), or augmented by N-acetyl cysteine (NAC, 4 mmol/L) in the perfusion buffer. Cardiac 64Cu retention from three 2-MBq bolus injections of 64Cu(ATSM) before and during hypoxia was then monitored by NaI detectors. Cardiac GSH content
The effect of photodynamic therapy (PDT) on neurons is of critical importance when treating cancers within or adjacent to the nervous system. Neurons show reduced sensitivity to meta-tetrahydroxyphenyl chlorin (mTHPC) mediated PDT, so the aim of this study was to investigate whether neuron sparing is due to endogenous cellular antioxidant activity. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to mTHPC-PDT in a 3D co-culture system following incubation with antioxidant inhibitors: diethyl dithiocarbamate (DDC, SOD-1 inhibitor), 2-methoxyestradiol (2-MeOH2, SOD-2 inhibitor) and l-buthionine sulfoximine (l-BSO, glutathione synthase inhibitor). Sensitivity of each cell type was assessed using a combination of live/dead staining and immunofluorescence. Pretreatment with DDC and with l-BSO significantly increased the sensitivity of neurons to mTHPC-PDT and also affected satellite glial cell viability, whereas 2-MeOE2 caused only a small increase in neuron ...
TY - JOUR. T1 - Protective effect of glutathione on the cytotoxicity caused by a combination of aluminum and iron in suspension-cultured tobacco cells. AU - Yamaguchi, Yukiko. AU - Yamamoto, Yoko. AU - Ikegawa, Hiroshi. AU - Matsumoto, Hideaki. PY - 1999/3. Y1 - 1999/3. N2 - The role of endogenous glutathione (GSH) in the protection of suspension-cultured tobacco cells from aluminum (Al) toxicity was examined. Cells at the logarithmic phase of growth were treated with or without A1 in nutrient medium prepared without P(i) and EDTA. In the absence of A1, total GSH content (including oxidized glutathione [GSSG]) increased gradually. In the presence of Al, the increase of GSH was repressed. This effect was observed before the loss of plasma membrane integrity and the loss of cell viability. In contrast, GSSG content in cells increased in the presence of A1. GSH-deprived cells were prepared by culturing cells with buthionine sulfoximine (an inhibitor of γ-glutamylcysteine synthetase) for 24 h. ...
Background: The role of mesenchymal stem cell in cellular therapy is the subject of interest for many researchers. The differentiation potential of MSCs and abilities in modulations of the recipients immune system makes them important cells in tissue regenerative studies. MSCs by releasing the proinflammatory cytokines play important role in immunomodulatory systems; however the signaling pathways for releasing of these mediators are not well understood. Glutathione has been shown to play a role in modulation of cytokines in hepatogenic differentiation. Objective: In the current study we aimed to investigate the effects of buthionine sulfoximine (BSO, inhibitor for glutathione synthesis) and N-acetylecystin (NAC, an inhibitor for ROS generation) on proinflammatory cytokines production in a hepatogenic differentiation model. Results: BSO and NAC significantly decreased IL-6 and TNF-α levels at 14 days of differentiation, whereas, NAC decreased the levels of IL-8 at days 2 and 14 of differentiation.
Arsenic trioxide (As2O3) has shown anti-tumour activity against a variety of solid tumours in vitro. However, the mechanisms responsible for its cytotoxicity against ovarian carcinoma remain elusive. In this thesis, the molecular determinants of its effects and factors mediating its chemoresistance in ovarian cancer cells were investigated. It was found that As2O3 treatment caused both apoptosis induction and caspase-independent cell death involving mitochondrial dysfunction. This was accompanied by endoplasmic reticulum stress induction and an increase in intracellular glutathione (GSH) level. The latter was in turn prevented by the concurrent use of GSH modulator, buthionine sulfoximine but not ascorbic acid. Gene expression analysis of arsenic-resistant OVCAR-3 (OVCAR-3/AsR) cells showed the involvement of multiple factors mediating its chemoresistance. Of particular interest, a genetic hub involving elevated interleukin 1A signalling was identified. This could consecutively modulate the ...
Villablanca JG, Volchenboum SL, Cho H, Kang MH, Cohn SL, Anderson CP, Marachelian A, Groshen S, Tsao-Wei D, Matthay KK, Maris JM, Hasenauer CE, Czarnecki S, Lai H, Goodarzian F, Shimada H, Reynolds CP. A Phase I New Approaches to Neuroblastoma Therapy Study of Buthionine Sulfoximine and Melphalan With Autologous Stem Cells for Recurrent/Refractory High-Risk Neuroblastoma. Pediatr Blood Cancer. 2016 08; 63(8):1349-56 ...
The pathophysiology of hepatic veno-occlusive disease is poorly understood. These studies were undertaken to determine the initial cellular target and the role of glutathione detoxification of dacarbazine, a toxin implicated in hepatic veno-occlusive disease. Sinusoidal endothelial cells (SECs) and hepatocytes were isolated and plated in culture dishes. Dacarbazine (5-(3,3-dimethyl-triazeno) imidazole-4-carboxamide), 3 and 6 mM, was toxic to SECs but not to hepatocytes. Onset of toxicity occurred between 11 and 12 hr as determined by serial MTT assays and ethidium homodimer dye exclusion. Glutathione detoxification of dacarbazine in SECs was suggested by: (1) depletion of glutathione before onset of toxicity; (2) exacerbation of toxicity by buthionine sulfoximine (BSO) depletion of glutathione; and (3) protection by exogenous glutathione. Protection by exogenous glutathione may be by uptake of intact tripeptide rather than by extracellular hydrolysis: neither acivicin (inhibitor of ...
For the studies using the isPRL model in anesthetized rats, UDCA was administered through the femoral vein to (1) normal Wistar rats (40, 60, and 80 μmol/hour), (2) rats with. depletion of liver glutathione after 2 days of treatment with buthionine sulfoximine (BSO; Sigma; UDCA at 80 μmol/hour), and (3) ABCC2/Mrp2-deficient [transport mutant (TR−)] rats (UDCA at 80 μmol/hour). For specificity experiments, either cholic acid (CA) or tauroursodeoxycholic acid (TUDCA) was administered (80 μmol/hour each) instead of UDCA. To assess the direct effect of GSNO on biliary epithelium, this compound was injected through the common bile duct of isPRLs. At the end of the experiments, blood was extracted selleck products from the portal vein, and animals were sacrificed, the liver and the common bile duct both being stored at −80°C until use. Inhibition of NO synthesis was. assessed selleck chemicals with the IPRL model by the infusion of UDCA in the presence or absence of the NOS inhibitor ...
In this study, we developed an in vivo method to determine drug effects on oxidation-induced apoptosis in the zebrafish brain caused by treatment with l-hydroxyglutaric acid (LGA). We confirmed that LGA-induced apoptosis was caused by oxidation by examining the presence of an oxidative product, nitrotyrosine. Next, we examined the effects of 14 characterized neuroprotectants on LGA-treated zebrafish, including: d-methione (d-Met), Indole-3-carbinol, deferoxamine (DFO), dihydroxybenzoate (DHB), deprenyl, l-NAME (N(G)-nitro-l-arginine methyl ester), n-acetyl l-cysteine (l-NAC), 2-oxothiazolidine-4-carboxylate (OTC), lipoic acid, minocycline, isatin, cortisone, ascorbic acid and α-tocopherol. Eleven of 14 neuroprotectants and 7 of 7 synthetic anti-oxidants exhibit significant protection in zebrafish. Buthionine sulfoximine (BSO), used as a negative control, exhibited no significant protective effects. In addition, three blood-brain barrier (BBB) impermeable compounds exhibited no significant effects. Our
Glutathione deficiency can still be treated and restored to satisfactory levels once again. Knowing how to increase the glutathione in your body is the first step.
TY - JOUR. T1 - Dopamine toxicity in neuroblastoma cells. T2 - Role of glutathione depletion by L-BSO and apoptosis. AU - Stokes, Alan H.. AU - Lewis, Denise Y.. AU - Lash, Lawrence H.. AU - Gray Jerome, W.. AU - Grant, Ken W.. AU - Aschner, Michael. AU - Vrana, Kent E.. N1 - Funding Information: This work was supported by grants GM 38931 (KEV) and T32 DA 07246 (AHS). PY - 2000. Y1 - 2000. N2 - Dopamine (DA), while an essential neurotransmitter, is also a known neurotoxin that potentially plays an etiologic role in several neurodegenerative diseases. DA metabolism and oxidation readily produce reactive oxygen species (ROS) and DA can also be oxidized to a reactive quinone via spontaneous, enzyme-catalyzed or metal-enhanced reactions. A number of these reactions are cytotoxic, yet the precise mechanisms by which DA leads to cell death remain unknown. In this study, the neuroblastoma cell line, SK-N-SH, was utilized to examine DA toxicity under varying oxidant states. Cells pretreated with the ...
The phosphatidylinositol 3-kinase (PI3K) pathway is activated in chronic obstructive pulmonary disease (COPD), but the regulatory mechanisms for this pathway are yet to be elucidated. The aim of this study was to determine the expression and role of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the PI3K pathway, in COPD. PTEN protein expression was measured in the peripheral lung of COPD patients compared with smoking and nonsmoking controls. The direct influence of cigarette smoke extract (CSE) on PTEN expression was assessed using primary lung epithelial cells and a cell line (BEAS-2B) in the presence or absence of l-buthionine-sulfoximine (BSO) to deplete intracellular glutathione. The impact of PTEN knockdown by RNA interference on cytokine production was also examined. In peripheral lung, PTEN protein was significantly decreased in patients with COPD compared with the subjects without COPD (P | 0.001) and positively correlated with the severity of airflow
Egea, J., Fabregat, I., Frapart, Y. M., Ghezzi, P., Görlach, A., Kietzmann, T., Kubaichuk, K., Knaus, U. G., Lopez, M. G., Olaso-Gonzalez, G., Petry, A., Schulz, R., Vina, J., Winyard, P., Abbas, K., Ademowo, S., Afonso, C. B., Andreadou, I., Antelmann, H., Antunes, F., Aslan, M., Bachschmid, M. M., Barbosa, R. M., Belousov, V., Berndt, C., Bernlohr, D., Bertrán, E., Bindoli, A., Bottari, S. P., Brito, P. M., Carrara, G., Casas, A. I., Chatzi, A., Chondrogianni, N., Conrad, M., Cooke, M. S., Costa, J. G., Cuadrado, A., My-Chan Dang, P., De Smet, B., Debelec-butuner, B., Dias, I., Dunn, J. D., Edson, A. J., El Assar, M., El-Benna, J., Ferdinandy, P., Fernandes, A. S., Fladmark, K. E., Förstermann, U., Giniatullin, R., Giricz, Z., Görbe, A., Griffiths, H., Hampl, V., Hanf, A., Herget, J., Hernansanz-Agustín, P., Hillion, M., Huang, J., Ilikay, S., Jansen-Dürr, P., Jaquet, V., Joles, J. A., Kalyanaraman, B., Kaminskyy, D., Karbaschi, M., Kleanthous, M., Klotz, L-O., Korac, B., Korkmaz, K. S., ...
Glutathione plays a pivotal role in many key metabolic reactions in your body. Each of your cells contains glutathione, a substance created from three amino acids: cysteine, glutamate, and glycine. The bodys
This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV ...
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Answer your questions about predicting bulk material behavior and show you how to use Rocky DEM in your heavy equipment design processes, giving you crucial insights.
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Das GDNF-Gen kodiert einen von Glia-Zellen gebildeten neutrotrophischen Faktor der zusammen mit dem Produkt des RET-Gens die Bildung und Apoptose von Nervenzellen steuert. Mutationen führen zu verschiedenen autosomal dominanten Erkrankungen, dem zentralen Hypoventilationssyndrom, der Hirschsprung-Erkrankung und dem Phäochromozytom.. ...
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Im Online-Event (http://bit.ly/2rWcBJS), zu dem diese Slides gehören, wurde diskutiert, welche Besonderheiten sich in frei zugänglichen virtuellen Räumen des I…

No data available that match "buthionine sulfoximine"


All subjects had an osmotic pump fitted to their right ear and it received buthionine sulfoximine (BSO) at a dose of 15 mM ...
Buthionine sulfoximine reversed all of the above SelS-induced changes, do it credible. And while indoor seating capacity is ...
buthionine sulfoximine. *Butisol. *butobarbitone. *butoconazole. *butoconazole nitrate. *butopyronoxyl. *butorphanol. * ...
1as atg aurothioglucose bpd bronchopulmonary bso buthionine comparatively cysteines cytoprotection h1299 hyperoxia hyperoxic ... hyperoxic nitrosylation oxidoreductase peroxiredoxin pharmacologically redox relies simplification smallest sulfoximine thiol ... 1as atg aurothioglucose bpd bronchopulmonary bso buthionine comparatively cysteines cytoprotection h1299 hyperoxia ... nitrosylation oxidoreductase peroxiredoxin pharmacologically redox relies simplification smallest sulfoximine thiol thioredoxin ...
In this study we show that GSH depletion, produced with GSH synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO), induces ...
  • Dose response relationships were derived for inhibition of glutathione synthesis in CHO cells, and for depletion of glutathione in exponentially growing T98G and CHO cells, as a function of extracellular L-buthionine-S-sulfoximine concentration. (elsevier.com)
  • in this study, GSH was depleted by inhibition of glutamylcysteine synthetase using buthionine sulfoximine (BSO) treatment in Ht22, a neuronal cell line derived from mouse hippocampus. (biomedcentral.com)
  • In Vivo Inhibition of L-buthionine-(S,R)-sulfoximine-induced Cataracts" by Joshua W. Carey, Eylem Y. Pinarci et al. (mst.edu)
  • Irreversible inhibition by L-buthionine-(S,R)-sulfoximine (BSO) of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), induces intracellular accumulation of ROS and augments chemioxyexcitation and LPS-mediated release of interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). (nih.gov)
  • Inhibition of GSH synthesis by buthionine sulphoximine (BSO) significantly attenuated TQ-induced neuroprotective effects against CoCl2 in rats and in PC12 cells. (bireme.br)
  • Inhibition of gamma-glutamyl cysteine synthetase by buthionine sulfoximine (BSO) lowered cellular GSH and strongly potentiated MeHg-induced lipoperoxidation and cell death in neuron culture but had minimal effect in glial culture. (springer.com)
  • Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). (springer.com)
  • We have administered Buthionine sulfoximine (BSO) an inhibitor of gamma-glutamylcysteine synthetase to wild type and rd1 mice, an animal model of retinitis pigmentosa, to study its influence over retina development and retinal pathology. (arvojournals.org)
  • Buthionine sulfoximine (BSO) is a glutathione depleting agent that inhibits the enzyme gamma-glutamylcysteine synthetase which is required in the early steps of glutathione synthesis. (scirp.org)
  • Buthionine Sulphoximine is a gamma-glutamylcysteine synthetase inhibitor potentially for the treatment of solid tumors. (adooq.com)
  • We studied the potentiation of doxorubicin activity in these cells by buthionine sulfoximine (BSO), a specific inhib itor of 7-glutamy Icysteine synthetase, and by verapamil and frans-flupenthixol, agents which interact with P-glycoprotein. (elsevier.com)
  • Here we investigated whether L-buthionine-(S,R)-sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, alters endothelial and vascular smooth muscle injury in response to peroxynitrite in vitro and during endotoxic shock in vivo. (utmb.edu)
  • 5. In conclusion, our results demonstrate that L-buthionine-(S,R)-sulphoximine, an inhibitor of γ-glutamylcysteine synthetase enhances peroxynitrite- and endotoxic shock-induced vascular failure. (utmb.edu)
  • The glutathione (GSH) synthesis inhibitor, buthionine sulfoximine (BSO) was tested for cytotoxicity and thiol depletion in murine and human tumor cells in vitro, and for its antitumor activity and toxicity in vivo. (semanticscholar.org)
  • Augmentation of adriamycin, melphalan, and cisplatin cytotoxicity in drug-resistant and -sensitive human ovarian carcinoma cell lines by buthionine sulfoximine mediated glutathione depletion. (semanticscholar.org)
  • Glutathione depletion in tissues after administration of buthionine sulphoximine. (semanticscholar.org)
  • 1999, Depletion of glutathione by buthionine sulfoxine is cytotoxic for human neuroblastoma cell lines via apoptosis. (dgidb.org)
  • Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20( S )-camptothecin, SN-38 [7-ethyl-10-hydroxy-20( S )-camptothecin], topotecan, and 7-chloromethyl-10,11-methylenedioxy-20( S )-camptothecin (CMMDC). (aacrjournals.org)
  • It has previously been shown that the depletion of the intracellular GSH levels in T lymphocytes through treatment with dl -buthionine ( S , R )-sulfoximine (BSO) results in hyporesponsiveness due to the abrogation of the proximal TCR-mediated signaling events ( 17 ). (jimmunol.org)
  • Studies in which buthionine sulfoximine was used to deplete GSH show that GSH is required for normal intestinal function ( 25 ) and that depletion of GSH exaggerates growth suppressive effects of thiol oxidants ( 28 ). (physiology.org)
  • IL-4 toxin resistance in MRP1-overexpressing cells could be reversed by the MRP1 inhibitors probenecid or MK571 and were not affected by glutathione depletion by dl -buthionine- S,R -sulfoximine. (aacrjournals.org)
  • The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma. (harvard.edu)
  • Buthionine sulfoximine (BSO) can deplete glutathione and synergistically enhance in vitro sensitivity to the alkylating agent melphalan (L-PAM) for many neuroblastoma cell lines, but optimal use of this combination needs to be defined because clinical responses have been less frequent and not durable. (nih.gov)
  • OBJECTIVES: I. Describe the toxic effects of combined chemotherapy with buthionine sulfoximine (BSO) and melphalan (L-PAM) in pediatric patients with progressive neuroblastoma. (knowcancer.com)
  • The cytotoxicity of two drug combinations (buthionine sulfoximine + melphalan or fenretinide + safingol) was tested using both DIMSCAN and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and the wider dynamic range of DIMSCAN facilitated detection of synergistic interactions. (aacrjournals.org)
  • Background: L-Buthionine (S,R) sulfoximine (BSO) is an inhibitor of glutathione biosynthesis and has been used as an effective means of depleting glutathione from cells and tissues. (nebraska.edu)
  • Methionine Sulfoximine" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)
  • Below are the most recent publications written about "Methionine Sulfoximine" by people in Profiles. (umassmed.edu)
  • Treatment with 500 μ M l -buthionine sulfoximine (BSO), which inhibits GSH synthesis, reduced cellular GSH but did not lead to generation of ROI. (deepdyve.com)
  • Results and Conclusion: The observed cellular uptake t 1 2 of approximately 55 min, coupled with a previously reported, rapid in vivo clearance of buthionine sulfoximine, suggest that continuous infusion would be preferable to bolus dosing. (elsevier.com)
  • Effective concentrations of L-buthionine-S-sulfoximine (24 h exposure), required to lower cellular glutathione content to 50% of control (EC 50 ), were under 1 rum for both cell lines. (elsevier.com)
  • Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi. (conicyt.cl)
  • 1996, Suppression of plasma estradiol and progesterone concentrations by buthionine sulfoximine in female rats. (dgidb.org)
  • Methods: The anti- proliferative effects of paracetamol and buthionine sulfoximine BSO (a glutathione depleting agent) alone and in combination on the liver cancer cells HepG2 and normal rat hepatocytes were investigated by sulphorhodamine-B assay. (scirp.org)
  • Methods and Materials: In vitro: L-buthionine-S-sulfoximine uptake was determined in human glioblastoma cells (T98G)and NIH-3T3 cells using 35 S-labeled drug. (elsevier.com)
  • Preincubation of etoposide-resistant human MCF7 breast cancer cells (MCF7/VP) with buthionine sulphoximine (BSO) resulted in their sensitisation to etoposide and vincristine. (nebraska.edu)
  • The scientists used a drug called L-Buthionine sulfoximine on rat brain cells. (medicalnewstoday.com)
  • GSH depleting agents such as buthionine sulfoximine inhibit cell growth in cultured cells. (physiology.org)
  • Breast cancer cells can also be sensitized to estrogen-induced apoptosis through suppression of glutathione by BSO (L-buthionine sulfoximine). (biomedcentral.com)
  • The sensor permeates HEK 293 cells and an increase in fluorescence is observed on adding buthionine sulfoximine, an inhibitor of GSH synthesis. (mdpi.com)
  • We tested two different compounds that deplete primary cortical cultures containing both neurons and astrocytes of intracellular GSH, L -buthionine-sulfoximine (L-BSO), and diethyl maleate (DEM). (hindawi.com)
  • l -buthionine- S,R -sulfoximine (BSO), an inhibitor of GSH synthesis, was used to deplete tissue GSH levels. (aacrjournals.org)
  • Purpose: To develop dosing criteria for the use of L-buthionine-S-sulfoximine (active diastereoisomer) as a glutathione depletor in the clinic, using a pharmacodynamic and pharmacokinetic in vitro-in vivo approach. (elsevier.com)
  • Lowering of PC12 GSH content, via blockade of its synthesis with buthionine sulfoximine, however, led to a significantly decreased accumulation of exogenous [ 3 H]DA without affecting uptake of the acetylcholine precursor [ 14 C]choline. (jneurosci.org)
  • BH4 toxicity and the redox-activated apoptotic pathway were counteracted by the H 2 O 2 -scavengers catalase and N -acetylcysteine and enhanced by the GSH neo-synthesis inhibitor BSO (buthionine sulfoximine). (biochemj.org)
  • The addition of buthionine sulfoximine to the protozoal culture considerably reduced the concentration of trypanothione and had no effect upon the metallothionein concentration. (conicyt.cl)
  • In still another invention, mammals are treated for protozoal infections by systemic administration of L-buthionine-S-sulfoximine and agent that increases nitrosative stress. (google.com)
  • We added to class I HDACIs the glutathione-synthesis inhibitor buthionine sulfoximine (BSO), in an attempt to create an intracellular environment that would facilitate HIV-1 activation. (core.ac.uk)
  • In vivo: L-buthionine-S-sulfoximine biodistribution was determined in male nude mice carrying human glioblastomas (T98G) intracranialy, using 35 S-labelled drug infused subcutaneously by osmotic pump. (elsevier.com)
  • 1999, Zonisamide inhibits nitric oxide synthase activity induced by N-methyl-D-aspartate and buthionine sulfoximine in the rat hippocampus. (dgidb.org)
  • The amount of L-buthionine-S-sulfoximine in tissues (estimated from 35 S drug disposition) reached steady state within 8 h and was proportional to the rate of infusion. (elsevier.com)
  • Although the glutathione synthesis inhibitor buthionine sulfoximine potentiated the effect of doxorubicin and H 2 O 2 , the antioxidant N -acetylcysteine prevented induction of cell enlargement. (aspetjournals.org)
  • DL-Buthionine-(S,R)-sulfoximine (BSO) 500 mg/kg was administered intraperitoneally to male Wistar rats. (scirp.org)
  • Male Sprague-Dawley rats received tap water (control) and 30 mmol/L of l -buthionine sulfoximine (BSO), an oxidant, with and without 1 mmol/L of Tempol (antioxidant) for 2 weeks. (ahajournals.org)
  • Male Sprague-Dawley rats were treated with L-buthionine-sulfoximine (BSO) and sulforaphane for 4 weeks. (ahajournals.org)
  • Buthionine Sulfoximine" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • Buthionine sulfoximine reduced resistance to these drugs. (aspetjournals.org)
  • P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. (scielo.br)
  • KLF4-mediated resistance to cisplatin was found to be abrogated by treatment with buthionine sulfoximine, an inhibitor of GSH synthesis. (sigmaaldrich.com)
  • Buthionine sulfoximine may also be used to increase the sensitivity of parasites to oxidative antiparasitic drugs. (wikipedia.org)
  • Differential effects of l -buthionine sulfoximine and ethacrynic acid on glutathione levels and. (deepdyve.com)
  • We ascertained that l-buthionine-S,R-sulfoximine (BSO), a selective inhibitor of glutamate-cysteine ligase, inhibited LTC4 release. (sigmaaldrich.com)
  • Buthionine sulfoximine (BSO) is a sulfoximine derivative which reduces levels of glutathione and is being investigated as an adjunct with chemotherapy in the treatment of cancer. (wikipedia.org)
  • l-Buthionine (S,R) sulfoximine did not affect ethanol consumption, but serum ethanol levels in BSO-treated mice were nearly 6-fold lower than in mice given ethanol alone. (nebraska.edu)
  • The tissue glutathione levels of C57BL/6 mice were depleted by providing them with drinking water containing 20 mM buthionine sulfoximine (BSO). (cdc.gov)
  • l-Buthionine (S,R) sulfoximine administration also attenuated ethanol-induced steatosis, prevented the leakage of lysosomal cathepsins into the cytosol, and prevented the ethanol-elicited decline in proteasome activity. (nebraska.edu)
  • ACTIVITY REGULATION: Inhibited by L-buthionine-S-sulfoximine (L-S- CC BSO). (genome.jp)
  • Germ cell stage dependent activity of EMS was potentiated by both L-buthionine-sulfoximine (BSO) and 1,2- dibromoethane (106934) (EDB). (cdc.gov)
  • Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cancer cell lines and their modification by buthionine sulfoximine. (semanticscholar.org)
  • Novel agents include α-alkyl-S-alkyl-homocysteine sulfoximines wherein the α-alkyl contains 2 to 8 carbon atoms, and the S-alkyl- contains 1 to 10 carbon atoms. (google.com)
  • This graph shows the total number of publications written about "Buthionine Sulfoximine" by people in Harvard Catalyst Profiles by year, and whether "Buthionine Sulfoximine" was a major or minor topic of these publication. (harvard.edu)
  • Below are the most recent publications written about "Buthionine Sulfoximine" by people in Profiles. (harvard.edu)

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