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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.


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Journal ArticleDOI
09 Sep 2015-PLOS ONE
TL;DR: It is suggested that EBR promotes ER stress and induces apoptosis and downregulated calnexin and upregulated BiP and IRE1α expression levels and induced CHOP translocation from the cytoplasm to nucleus, which confirmed the alteration of the ER pathway due to drug treatment.
Abstract: Epibrassinolide (EBR) is a polyhydroxylated sterol derivative and biologically active compound of the brassinosteroids. In addition to well-described roles in plant growth, EBR induces apoptosis in the LNCaP prostate cancer cells expressing functional androgen receptor (AR). Therefore, it is suggested that EBR might have an inhibitory potential on androgen receptor signaling pathway. However, the mechanism by which EBR exerts its effects on LNCaP is poorly understood. To address this gap in knowledge, we used an unbiased global proteomics approach, i.e., stable-isotope labeling by amino acids in cell culture (SILAC). In total, 964 unique proteins were identified, 160 of which were differentially expressed after 12 h of EBR treatment. The quantification of the differentially expressed proteins revealed that the expression of the unfolded protein response (UPR) chaperone protein, calreticulin (CALR), was dramatically downregulated. The decrease in CALR expression was also validated by immunoblotting. Because our data revealed the involvement of the UPR in response to EBR exposure, we evaluated the expression of the other UPR proteins. We demonstrated that EBR treatment downregulated calnexin and upregulated BiP and IRE1α expression levels and induced CHOP translocation from the cytoplasm to nucleus. The translocation of CHOP was associated with caspase-9 and caspase-3 activation after a 12 h EBR treatment. Co-treatment of EBR with rapamycin, an upstream mTOR pathway inhibitor, prevented EBR-induced cell viability loss and PARP cleavage in LNCaP prostate cancer cells, suggesting that EBR could induce ER stress in these cells. In addition, we observed similar results in DU145 cells with nonfunctional androgen receptor. When proteasomal degradation of proteins was blocked by MG132 co-treatment, EBR treatment further induced PARP cleavage relative to drug treatment alone. EBR also induced Ca2+ sequestration, which confirmed the alteration of the ER pathway due to drug treatment. Therefore, we suggest that EBR promotes ER stress and induces apoptosis.

16 citations

Journal ArticleDOI
TL;DR: It is demonstrated that hydrogen peroxide-induced oxidative stress regulates the activity of the anti-apoptotic protein Akt via the ubiquitin-proteasome degradation system and that H2O2-induced cytotoxicity was mediated by active Akt degradation.
Abstract: Akt is a well-established protein that regulates cell growth, survival and anti-apoptotic mechanisms. In this study, we demonstrated that hydrogen peroxide (H2O2)-induced oxidative stress regulates the activity of the anti-apoptotic protein Akt via the ubiquitin-proteasome degradation system. H2O2 induced cytotoxicity in PC12 cells and decreased the cellular protein and phosphorylation levels of Akt in a concentration- and exposure time-dependent manner. This downregulation was blocked by the proteasome inhibitor MG132 and the Akt-specific inhibitor LY294002. In addition, an in vivo ubiquitination assay revealed that the degradation of Akt was mediated by the ubiquitin-mediated proteasome pathway and further demonstrated that this ubiquitination was dependent on the phosphorylation status of Akt. Furthermore, the exogenously overexpressed active form of Akt, but not its inactive form, induced resistance to H2O2-mediated cell death. These results suggested that H2O2-induced cytotoxicity was mediated by active Akt degradation.

16 citations

Journal ArticleDOI
TL;DR: Investigation of whether and how proteasome activity changes in Saccharomyces cerevisiae cells undergoing PCD as a result of treatment with acetic acid shows that proteasomesome activation starts 60 min after AA-PCD induction, with a maximum at 90 min, and decreases at 150 min.
Abstract: To gain further insight into the mechanism by which yeast programmed cell death (PCD) occurs, we investigated whether and how proteasome activity changes in Saccharomyces cerevisiae cells undergoing PCD as a result of treatment with acetic acid (AA-PCD) We show that proteasome activation starts 60 min after AA-PCD induction, with a maximum at 90 min, and decreases at 150 min Moreover, cell survival measurements carried out in the absence or presence of MG132, which inhibits proteasome function, show that the inhibition of proteasome activity partially prevents AA-PCD, thus indicating that a transient proteasome activation is needed for AA-PCD to occur

16 citations

Journal ArticleDOI
TL;DR: Dihydrotanshinone I (DHT), a bioactive compound in Salvia miltiorrhiza, was reported to exhibit cytotoxicity against various malignancies as mentioned in this paper .

16 citations

Journal ArticleDOI
TL;DR: In this paper, the authors determined whether nuclear factor-kappaB and tumor necrosis factor-alpha (TNF-alpha) play role in the formation of gastric ulcer induced by phorbol-12-myristate-13-alphacetate (PMA) in rats.
Abstract: Phorbol esters induce inflammation in rodents by activating protein kinase C. We determined whether nuclear factor-kappaB (NF-kappaB) and tumor necrosis factor-alpha (TNF-alpha) play role in the formation of gastric ulcer induced by phorbol-12-myristate-13-alphacetate (PMA) in rats. Subserosally injected PMA dose-dependently induced gastric mucosal ulcer. Activation of NF-kappaB in the gastric mucosa corresponding to the PMA injection sites was observed before the ulcers became obvious as assessed by an in situ fluorescence DNA binding assay and electrophoretic mobility shift assay. The NF-kappaB activation and subsequent ulcer formation were significantly inhibited by injection of pyrrolidine dithiocarbamate, proteasome inhibitor (MG132), or NF-kappaB decoy. Antibody against TNF-alpha significantly inhibited ulcer formation without attenuating NF-kappaB activation. These results suggest that both NF-kappaB activation followed by TNF-alpha release contribute to tissue damage in PMA-induced gastric ulcer formation.

16 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202386
202270
202157
202059
201962
201848