Search results for "sulfoximine"
showing 10 items of 32 documents
Opposite Effects of Mechanical Action of Fluid Flow on Proangiogenic Factor Secretion From Human Adipose-Derived Stem Cells With and Without Oxidativ…
2017
Mechanical forces, hypoxia, and oxidative stress contribute to skin renewal, perfusion, and wound healing, but how are they regulating subcutaneous adipose-derived stem cells (ASCs) in the inflammatory microenvironment associated to skin repair and disorders is unknown. In this study, ASCs were isolated from lipoaspirate samples from plastic surgery patients, primary cultured and their differentiation and secretion of a panel of cytokines with pronounced effects on skin repair and angiogenesis were studied under mechanical stimulation by intermittent fluid flow, 1% hypoxia and oxidative stress by glutathione (GSH) depletion with buthionine sulfoximine (BSO) treatment. Mechanical action of f…
Effect of Buthionine Sulfoximine on the Sensitivity to Doxorubicin of Parent and MDR Tumor Cell Lines
1994
We have studied the interaction of glutathione-depleting concentrations of buthionine sulfoximine (BSO) with the anti-proliferative activity of doxorubicin (DXR) in three tumor lines, the mouse B16 melanoma. Friend erythroleukemia and the human K562 leukemia, both as DXR-sensitive and-resistant (with typical multidrug resistance) variants. BSO significantly enhanced the DXR effects in the wild-type Friend and K562 leukemias, and especially in the drug-resistant subline of Friend leukemia. BSO did not modify DXR accumulation and retention in the latter clone. Moreover, neither BSO nor verapamil used alone completely reversed the resistance to DXR of this cell line; their combination was more…
Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation
2021
Congenital malformations are a common adverse outcome in pregnancies complicated by pregestational obesity, although the underlying mechanisms are still unrevealed. Our aim was to study the effect of oxidative stress in obesity-induced teratogenesis. Wistar rats were fed a high-fat diet for 13 weeks, with (OE group) or without (O group) vitamin E supplementation. Then, rats were mated and sacrificed at day 11.5 of gestation. Embryos from O dams presented a 25.9 ± 3.5% rate of malformations (vs. 8.7 ± 3.4% in C rats), which was reduced in the OE group (11.5 ± 2.3%). Pregestational obesity induced hepatic protein and DNA oxidation and a decline in antioxidant enzymes. Importantly, glutathione…
Antiproliferative and chemomodulatory effects of interferon-γ on doxorubicin-sensitive and -resistant tumor cell lines
1993
Biological agents might offer various therapeutic opportunities in the treatment of cancer, including a direct and/or host-mediated antiproliferative effect and also the possibility to favorably modulate tumor resistance to antineoplastic drugs. We studied the in vitro antiproliferative effects of interferon (IFN)-gamma on the mouse B16 melanoma and Friend erythroleukemia, and the human K562 erythroleukemia, as doxorubicin (DXR)-sensitive and -resistant (multidrug resistant) variants. These effects were marked in B16 melanoma and rather slight in K562 erythroleukemia, without any difference between the DXR-sensitive and -resistant lines. The chemosensitive variant of Friend erythroleukemia …
Effect of nonprotein thiols on protein synthesis in isolated rat hepatocytes.
1996
The ability of nonprotein thiols to modulate rates of protein synthesis was investigated in isolated rat hepatocytes. Addition of cysteine stimulates protein labelling by [14C]Leucine. Glutathione depletion, induced by in vivo administration of L-buthionine sulfoximine and diethylmaleate, did not alter the effect of cysteine, although it decreased the rate of protein synthesis by 32%. The effect of cysteine on protein synthesis does not seem to be related to a perturbation of the redox state of the NAD+/NADH system or to changes in the rate of gluconeogenic pathway. The following observations indicate that cysteine may stimulate protein synthesis by increasing intracellular levels of aspart…
Glutathione metabolism in primary astrocyte cultures: flow cytometric evidence of heterogeneous distribution of GSH content.
1993
The time-course of intracellular glutathione (GSH) values after incubation with L-buthionine-(S,R)-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, showed that glutathione turns over with a half-life of 5 h. Intracellular GSH was assayed by flow cytometry using three different methods. Astrocytes showed a narrow range of cellular size but a wide range of intracellular GSH. This heterogeneity was resolved into three distinct subpopulations which represent 20%, 35% and 45% of the total astrocyte number. The less abundant subpopulation had the lower GSH content, while the most abundant was the subpopulation with the higher content. Over 95% of astrocytes were in t…
Glutathione metabolism in skeletal muscle derived cells of the L6 line
1993
Skeletal muscle derived L6 myoblasts possess a considerably high resting total glutathione (TGSH) pool. Exposure to L-buthionine-[S,R]-sulphoximine resulted in a 90% depletion of the intracellular TGSH pool. All the key enzymes of glutathione metabolism, especially glutathione S-transferase, were observed to be considerably active in the undifferentiated cells. Se-dependent glutathione peroxidase activity appeared to account for most of the total GSH peroxidase activity of the cells. A significant contribution of gamma-glutamyl transpeptidase-independent (5 mM acivicin insensitive) mechanism to the extracellular GSH uptake capacity of the muscle cells was evident. Efflux of oxidized glutath…
Inhibition of liver trans-sulphuration pathway by propargylglycine mimics gene expression changes found in the mammary gland of weaned lactating rats…
2003
In the lactatingmammary gland, weaning produces mitochondrial cytochrome c release and nuclear DNA fragmentation, as determined by gel electrophoresis. This is followed by a significant decrease in lactation. Weaning for 2 h produces an early induction of the tumour suppressor/transcription factor p53, whereas the oncoprotein c-Jun and c-Jun N-terminal kinase are elevated after 24 h of weaning when compared with controls. The expression of p21cip1 and p27kip1, cyclin-dependent kinase inhibitors, was significantly higher in weaned rats when compared with control lactating rats. All the changes mentioned above also happen in the lactatingmammary gland when propargylglycine, an inhibitor of th…
Influence of glutathione levels and heat-shock on the steady-state levels of oxidative DNA base modifications in mammalian cells
1999
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 ef…
Lack of nucleophilic addition in the isoxazole and pyrazole diketone modified analogs of curcumin; implications for their antitumor and chemosensitiz…
2009
Curcumin (CUR) can be considered as a good lead compound for the design of new anticancer drugs. Further, structure-activity relationship studies may clarify the importance of the redox activities in the antitumor effects of the drug. We have elaborated the alpha,beta-unsaturated 1,3-diketone moiety of CUR into the isoxazole (ISO) and pyrazole (PYR) derivatives. These derivatives should be much less prone to nucleophilic addition than CUR and benzyl mercaptan addition analyses showed that indeed they do not form isolable conjugated products. When compared with CUR, ISO and PYR exhibited increased cell growth inhibitory and pro-apoptotic effects in liver cancer HA22T/VGH cells as well as in …