Topic
MG132
About: MG132 is a research topic. Over the lifetime, 1499 publications have been published within this topic receiving 56589 citations. The topic is also known as: MG132 & Z-Leu-leu-leu-al.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: It is suggested that ursolic acid induces apoptosis via activation of caspase and phosphorylation of GSK 3β in SK-OV-3 cancer cells as a potent anti-cancer agent for ovarian cancer therapy.
Abstract: Although ursolic acid isolated from Oldenlandia diffusa (Rubiaceae) was known to have anticancer activities in prostate, breast and liver cancers, the underlying mechanism of ursolic acid in ovarian cancer cells was not investigated so far. In the present study, the apoptotic mechanism of ursolic acid was elucidated in SK-OV-3 ovarian cancer cells by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay, cell cycle analysis and Western blotting. Ursolic acid exerted cytotoxicity against SK-OV-3 and A2780 ovarian cancer cells with IC₅₀ of ca. 50 and 65 µM, respectively. Apoptotic bodies were observed in ursolic acid treated SK-OV-3 cells. Also, ursolic acid significantly increased ethidium homodimer stained cells and sub-G1 apoptotic portion in SK-OV-3 cells. Consistently, Western blotting revealed that ursolic acid effectively cleaved poly(ADP-ribose) polymerase (PARP), caspase-9 and -3, suppressed the expression of survival genes such as c-Myc, Bcl-x(L) and astrocyte elevated gene (AEG)-1, and upregulated phosphorylation of extracellular signal-regulated kinase (ERK) in SK-OV-3 cells. Interestingly, ursolic acid suppressed β-catenin degradation as well as enhanced phosphorylation of glycogen synthase kinase 3 beta (GSK 3β). Furthermore, GSK 3β inhibitor SB216763 blocked the cleavages of caspase-3 and PARP induced by ursolic acid and proteosomal inhibitor MG132 disturbed down-regulation of β-catenin, activation of caspase-3 and decreased mitochondrial membrane potential (MMP) induced by ursolic acid in SK-OV-3 cells. Overall, our findings suggest that ursolic acid induces apoptosis via activation of caspase and phosphorylation of GSK 3β in SK-OV-3 cancer cells as a potent anti-cancer agent for ovarian cancer therapy.
47 citations
•
TL;DR: Proteasome inhibitors like MG132, PSI, II and III (MG262) have been shown to block both TNF-alpha-associated up-regulation of the H CMV IE1/2 enhancer/promoter in monocytic cells in an in vitro transient transfection system and HCMV replication in permissive embryonal fibroblasts, which suggests that ganciclovir-resistant HCMv strains are sensitive to proteasome inhibition.
Abstract: Recently, we like others, demonstrated that systemic inflammation is the most important mechanism involved in (re)activation of human cytomegalovirus (HCMV) in both immunocompetent patients. By in vitro studies the eukaryotic transcription factor NF-kappaB could be identified as the key mediator of TNF-alpha- and IE1-dependent stimulation of the HCMV IE1/2 enhancer/promoter activity, which is crucial for initiation of viral gene expression during reactivation from latency as well as productive infection. The enzymatic proteasome complex plays a central role in regulating intracellular processes, including the activation of NF-kappaB. As present antiviral strategies target mainly late events in HCMV replication (DNA replication, virus assembly) that do not completely prevent virus mediated immunopathogenesis, we wondered whether proteasome inhibitors might be a novel tool for targeting the interaction between inflammation and HCMV (re)activation. Here, proteasome inhibitors like MG132, PSI, II and III (MG262) have been shown to block both TNF-alpha-associated up-regulation of the HCMV IE1/2 enhancer/promoter in monocytic cells in an in vitro transient transfection system and HCMV replication in permissive embryonal fibroblasts. Importantly, ganciclovir-resistant HCMV strains are sensitive to proteasome inhibitors. The effect of proteasome inhibitors on HCMV replication was found to be specific as replication of other herpes viruses, like HSV-1 and HSV-2, under identical experimental conditions was not influenced. Inhibition of HCMV replication correlated with a delayed and significantly reduced expression of IE proteins, particularly of the IE2 protein, suggesting that MG132 blocks HCMV replication at an immediate early stage of infection. Early and late protein synthesis as shown exemplary for the pp52 (DNA-binding protein) and p68 (structural protein) protein production and viral DNA synthesis were also inhibited. Suppression of HCMV replication could be correlated with an increased cytosolic accumulation of IkappaB as well as a reduced NF-kappaB binding activity in nuclear extracts of MG132-treated cells, which mainly regards NF-kappaB p50. MG132 also reduced the immune modulatory activity of the virus by abrogating virus-induced up-regulation of cellular ICAM-1. These data suggest that short-term therapy with proteasome inhibitors might be an alternative strategy to prevent (re)activation, replication and immune modulatory activity of HCMV in patients with systemic inflammation.
46 citations
••
TL;DR: Pressure-induced activation of the UPP leads to transcription of IL-6 driven by NFkappaB, and together with precedence in the literature, these data suggest that pressure-induced Activation of The ubiquitin/proteasome pathway leads to Regulation of interleukin (IL)-6 by retinal glia.
Abstract: PURPOSE. To investigate how hydrostatic pressure influences regulation of interleukin (IL)-6 by retinal glia and whether this regulation is associated with the ubiquitin/proteasome pathway (UPP) and activation of the transcription factor nuclear factor (NF)B. METHODS. Astrocytes and microglia isolated from rat retina were maintained in vitro, and the IL-6 concentration in the media at ambient and elevated pressure were compared, with and without the proteasome inhibitor MG132 (10 M). Immunocytochemistry was used to correlate translocation of NFB with pressure. RESULTS. Exposure to elevated pressure for 24 hours maximally altered the concentration of media IL-6 of glia cultures, where IL-6 concentrations decreased in astrocyte cultures and increased in microglia cultures. These pressure-induced changes in IL-6 were largely insensitive to MG132 in astrocytes, but were largely MG132-sensitive in microglia. Like IL-6 regulation, pressure-induced activation of NFB also differed between the two glial cell types, where nuclear localization of NFB was transient in astrocytes, but sustained in microglia. Elevated pressure also increased MG132-sensitive expression of IL-6 mRNA by microglia. CONCLUSIONS. Though pressure-induced regulation of IL-6 by astrocytes is preceded by NFB translocation, it is not altered by MG132 and therefore is not likely to be regulated by NFB or the UPP. In contrast, pressure-induced regulation of IL-6 protein and mRNA by microglia is preceded by NFB translocation and is sensitive to MG132. Together with precedence in the literature, these data suggest that pressure-induced activation of the UPP leads to transcription of IL-6 driven by NFB. (Invest Ophthalmol Vis Sci. 2006;47:3860‐3869) DOI:10.1167/ iovs.05-1408
46 citations
••
TL;DR: It is proved that reFIP-gts entry into the cell and localization in endoplasmic reticulum can result in ER stress, thereby increasing ER stress markers (CHOP/GADD153) and intracellular calcium release in A549 cells and strongly suggest that ER stress induces intrace cellular calcium release and results in inhibition of telomerase activity.
46 citations
••
TL;DR: The results demonstrate the anti-bladder-tumor properties of the natural compound baicalein which shows a slight anti- Bladder-Tumor effect in vivo.
Abstract: Some phytochemicals with the characteristics of cytotoxicity and/or antimetastasis have generated intense interest among the anticancer studies. In this study, a natural flavonoid baicalein was evaluated in bladder cancer in vitro and in vivo. Baicalein inhibits 5637 cell proliferation. It arrests cells in G1 phase at 100 μM and in S phase below 75 μM. The protein expression of cyclin B1 and cyclin D1 is reduced by baicalein. Baicalein-induced p-ERK plays a minor role in cyclin B1 reduction. Baicalein-inhibited p65NF-κB results in reduction of cell growth. Baicalein-induced pGSK(ser9) has a little effect in increasing cyclin B1/D1 expression instead. The translation inhibitor cycloheximide blocks baicalein-reduced cyclin B1, suggesting that the reduction is caused by protein synthesis inhibition. On the other hand, neither cycloheximide nor proteasome inhibitor MG132 completely blocks baicalein-reduced cyclin D1, suggesting that baicalein reduces cyclin D1 through protein synthesis inhibition and proteasomal degradation activation. In addition, baicalein also inhibits cell invasion by inhibiting MMP-2 and MMP-9 mRNA expression and activity. In mouse orthotopic bladder tumor model, baicalein slightly reduces tumor size but with some hepatic toxicity. In summary, these results demonstrate the anti-bladder-tumor properties of the natural compound baicalein which shows a slight anti-bladder-tumor effect in vivo.
46 citations