MG-132
(Synonyms: MG132,蛋白酶体抑制剂,MG132,Z-LLL-al,Z-Leu-Leu-Leu-CHO) 目录号 : GC10383
MG-132是一种强效、可逆和细胞渗透的蛋白酶体抑制剂，属于合成肽醛类。
Cas No.:133407-82-6
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
Clarification of FBW7 as the E3 ubiquitin ligase of cPLA2 protein. (C) DLD1WT cell was treated with 50μM MG132 for 6h and then blotted with cPLA2 antibody.
DLD1WT cell was treated with MG132(50μM, for 6h) (GlpBio, USA).
Cell Reports Medicine (2024). PMID: 38614093 IF: 14.2994 -
Related Biological Data
Silent information regulator 2 (SIRT2) increased glucose 6-phosphate dehydrogenase. A, B, G6PD protein expression levels were analyzed by western blot analysis in stably transfected ACHN and Caki-1 cells following treatment with 100 μg/mL cycloheximide (CHX) with or without 10 μg/mL MG132 for 0, 6, 9, 12h.
Proteasome inhibitor MG132 (#GC10383; GLPBIO) powder was dissolved in DMSO to prepare 10 mg/mL storage solution.
Cancer Science (2021). PMID: 34310804 IF: 6.712 -
Related Biological Data
Depletion of TgATG7 results in TgATG8 degradation through ubiquitin-proteasome system. (G) HA-TgATG8 was co-expressed along with either FLAG-UbWT or FLAG-UbKO and its stability was monitored in the presence or absence of CHX and MG132 using anti-HA antibody.
The stability of endogenous TgATG8 protein was tested with or without the addition of CHX (10 μg/ml) and MG132 (15μM) (GlpBio, USA).
Bba-Mol Basis Dis (2023): 166891. PMID: 37739091 IF: 6.2001 -
Related Biological Data
DHA reduces DNMT1 and enhances Klotho levels. h Representative Western blot analyses of DNMT1 expression are shown in primary mouse renal tubular cells(PRTCs).
Primary mouse renal tubular cells(PRTCs) were treated with TGF-β (10ng/mL) and DHA (10μM) in combination with MG132(0.5µM)(GlpBio, USA), E64d (10µg/mL), or ammonium chloride (NHCl; 1mM) for 24 h.
Acta Pharmacologica Sinica (2022): 1-15. PMID: 35347248 IF: 6.1496 -
Related Biological Data
PHLDA1 regulates YWHAE levels through proteasomal degradation pathways. (A, B) Western blot analysis of YWHAE expression; cells were treated with MG132 alone or MG132+6% CSE.
Moreover, the reduction of YWHAE level caused by CSE or PHLDA1 siRNA could be rescued by MG132(GlpBio, USA), a proteasome inhibitor.
Int J Biochem Cell B (2022): 106297. PMID: 36108948 IF: 5.6521 -
Related Biological Data
Increased apoptosis induced by VRK1 depletion is driven by DNA-PK instability. (E) OVCAR-4 cells were treated with 2μM of VRK1 inhibitor. After 24 h, the cells were treated with MG132 (50μg/ml) for 6h. After treatment, cells were harvested and subjected to DNA-PK IP and ubiquitination was analyzed using western blotting.
Cells were treated with 50μg/ml MG132 (cat. no. GC10383, GLPBIO, CA, USA) for 6h.
Experimental Cell Research (2024): 114036. PMID: 38614421 IF: 3.7001
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| Cell experiment [1]: | |
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Cell lines |
KIM-2 |
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Preparation Method |
MG-132 were diluted in Me2SO. Cells were treated with protease inhibitors or dilutant alone. Supernatant and monolayer cells were harvested by centrifugation and fixed in 70% ethanol in PBS for staining with acridine orange. Equal volumes of cells and acridine orange (5 mg/ml in PBS) were mixed on a microscope slide and examined by fluorescence microscopy. |
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Reaction Conditions |
0, 1.5, 5 μM, 24 h |
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Applications |
MG-132 treatment induces apoptosis in a cell cycle dependent manner. |
| Animal experiment [2]: | |
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Animal models |
C57BL/10ScSn DMD mdx mice |
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Preparation Method |
Localized administration was performed by injection of MG-132 into the gastrocnemius muscles of mdx mice. To visualize the injected muscle, MG-132 (final concentration of 20 μmol/L) was pre-mixed with 1% India ink in phosphate-buffered saline (PBS) for a total volume of 100 μl. Mice were sacrificed 24 hours after injection, and skeletal muscles were quickly isolated for further analysis. To systemically administer MG-132, Alzet Minipumps was subcutaneously implanted in the anterior back region of mdx mice. Experiments were conducted on 6-month-old mdx mice. For 8 days, administration of either different concentrations of MG-132 (delivered at rate of either 1 μg, or 5 μg or 10 μg/kg/24 hours) or the inhibitor-diluent (PBS only) was enforced, as a negative control. Skeletal muscle tissues were collected from untreated (PBS only) and MG-132-treated mdx mice for further analysis. |
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Dosage form |
1 μg, 5 μg, 10 μg/kg, injection into the gastrocnemius muscles or subcutaneously implanted Alzet Minipumps |
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Applications |
MG-132, as a proteasomal inhibitor, effectively rescues the expression levels and plasma membrane localization of dystrophin, β-dystroglycan, α-dystroglycan, and α-sarcoglycan in skeletal muscle fibers from mdx mice. Furthermore, MG-132 reduces muscle membrane damage, as revealed by vital staining of the diaphragm and gastrocnemius muscle isolated from treated mdx mice, and ameliorates the histopathological signs of muscular dystrophy, as judged by hematoxylin and eosin staining of muscle biopsies taken from treated mdx mice. |
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References: [1]. Tsubuki, S et al. Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine. Journal of biochemistry vol. 119,3 (1996): 572-6. [2]. MacLaren, A P et al. p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells. Cell death and differentiation vol. 8,3 (2001): 210-8. [3]. Bonuccelli, Gloria et al. Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. The American journal of pathology vol. 163,4 (2003): 1663-75. |
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MG-132 is a potent, reversible, and cell-permeable proteasome inhibitor. It belongs to the class of synthetic peptide aldehydes. It reduces the degradation of ubiquitin-conjugated proteins in mammalian cells and permeable strains of yeast by the 26S complex without affecting its ATPase or isopeptidase activities.MG-132 activates c-Jun N-terminal kinase (JNK1), which initiates apoptosis.MG-132 also inhibits NF-κB activation and prevents β-secretase cleavage.
MG-132 inhibits 20S proteasome with IC50 of 100 nM in vitro. Furthermore,MG-132 treatment induces apoptosis in a cell cycle dependent manner.[1][2]
MG-132 can treat mdx Mice by rescuing the Expression and Membrane Localization of Dystrophin and Dystrophin-Associated Proteins. For in vivo experiment,MG-132 was administrated into mdx mice by injection into the gastrocnemius muscles or subcutaneously implanted Alzet Minipumps. As a result,MG-132, as a proteasomal inhibitor, effectively rescues the expression levels and plasma membrane localization of dystrophin, β-dystroglycan, α-dystroglycan, and α-sarcoglycan in skeletal muscle fibers from mdx mice. Furthermore,MG-132 reduces muscle membrane damage, as revealed by vital staining of the diaphragm and gastrocnemius muscle isolated from treated mdx mice, and ameliorates the histopathological signs of muscular dystrophy, as judged by hematoxylin and eosin staining of muscle biopsies taken from treated mdx mice.[3]
References:
[1]. Tsubuki, S et al. Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine. Journal of biochemistry vol. 119,3 (1996): 572-6.
[2]. MacLaren, A P et al. p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells. Cell death and differentiation vol. 8,3 (2001): 210-8.
[3]. Bonuccelli, Gloria et al. Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. The American journal of pathology vol. 163,4 (2003): 1663-75.
MG-132是一种强效、可逆和细胞渗透的蛋白酶体抑制剂，属于合成肽醛类。它可以减少哺乳动物细胞和可渗透的酵母菌株中26S复合物对泛素结合蛋白的降解，而不影响其ATPase或异构肽酶活性。MG-132激活c-Jun N末端激酶（JNK1），从而引发细胞凋亡。此外，MG-132还能抑制NF-κB的激活并防止β秘密酶裂解作用。
MG-132在体外的IC50为100纳摩尔，可以抑制20S蛋白酶。此外，MG-132处理会以细胞周期依赖性方式诱导凋亡。
MG-132可以通过挽救Dystrophin和Dystrophin相关蛋白的表达和膜定位来治疗mdx小鼠。在体内实验中，MG-132被注射到腓肠肌或皮下植入Alzet微型泵中进行治疗。结果显示，作为一种蛋白酶体抑制剂，MG-132有效地挽救了mdx小鼠骨骼肌纤维中Dystrophin、β-dystroglycan、α-dystroglycan和α-sarcoglycan的表达水平和质膜定位。此外，MG-132减少了肌肉膜损伤，在经过处理的mdx小鼠隔膜和腓肠肌的活性染色中得以证实，并改善了肌萎缩的组织学病理学特征，在经过处理的mdx小鼠取样后用苏木精伊红染色判断出来。[3]
| Cas No. | 133407-82-6 | SDF | |
| 别名 | MG132,蛋白酶体抑制剂,MG132,Z-LLL-al,Z-Leu-Leu-Leu-CHO | ||
| 化学名 | benzyl N-[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]carbamate | ||
| Canonical SMILES | CC(C)CC(C=O)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)OCC1=CC=CC=C1 | ||
| 分子式 | C26H41N3O5 | 分子量 | 475.6 |
| 溶解度 | ≥ 23.78mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1026 mL | 10.513 mL | 21.0261 mL |
| 5 mM | 0.4205 mL | 2.1026 mL | 4.2052 mL |
| 10 mM | 0.2103 mL | 1.0513 mL | 2.1026 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
MG-132 attenuates cardiac deterioration of viral myocarditis via AMPK pathway
Background: Coxsackievirus B3 (CVB3) is the primary cause of infectious myocarditis. Aggressive immunological activation and apoptosis of myocytes contributes to progressive dysfunction of cardiac contraction and poor prognosis. MG-132, a proteasome inhibitor, regulates mitochondrial-mediated intrinsic myocardial apoptosis and downregulates NF-κB-mediated inflammation. Here, we determined whether AMPK pathway participates in MG-132-mediated myocardial protection in viral-induced myocarditis. Methods and results: Acute viral myocarditis models were established by intraperitoneal inoculation of CVB3 in male BALB/c mice. Myocarditis and age-matched control mice were administered MG-132 and/or BML-275 dihydrochloride (BML) (AMPK antagonist) intraperitoneally daily from the day following CVB3 inoculation. MG-132 improved hemodynamics and inhibited the structural remodeling of the ventricle in mice with myocarditis, while BML largely blunted these effects. TUNEL staining and immunochemistry suggested that MG-132 exerts anti-apoptotic and anti-inflammatory effects against CVB3-induced myocardial injuries. BML attenuated the effects of MG-132 on anti-apoptosis and anti-inflammation. Conclusion: MG-132 modulated apoptosis and inflammation, improved hemodynamics, and inhibited the structural remodeling of ventricles in a myocarditis mouse model via regulation of the AMPK signal pathway.
MG-132 interferes with iron cellular homeostasis and alters virulence of bovine herpesvirus 1
Bovine herpesvirus 1 (BoHV-1) requires an iron-replete cell host to replicate efficiently. BoHV-1 infection provokes an increase in ferritin levels and a decrease of transferrin receptor 1 (TfR-1) expression, ultimately lowering iron pool extent. Thus, cells try to limit iron availability for virus spread. It has been demonstrated that MG-132, a proteasome inhibitor, reduces BoHV-1 release. Since ferritin, the major iron storage protein in mammalian cells, undergoes proteasome-mediated degradation, herein, the influence of MG-132 on iron metabolism during BoHV-1 infection was examined. Following infection in bovine cells (MDBK), MG-132 reduced cell death and viral yield. Western blot analysis showed a significant ferritin accumulation, likely due to the inhibition of its proteasome-mediated degradation pathway. In addition, the concomitant down-regulation of TfR-1 expression, observed during infection, was counteracted by proteasome inhibitor. This trend may be explained by enhanced acidic vesicular organelles, detected by acridine orange staining, determining a reduction of intracellular pH, that promotes new synthesis of TfR-1 degraded in a recycling pathway. In addition, MG-132 influences cellular iron distribution during BoHV-1 infection, as revealed by Perls' Prussian blue staining. However, cellular iron content, evaluated by Atomic Absorption Spectrophotometry, resulted essentially unaltered. These findings reveal that MG-132 may contribute to limit cellular iron availability for virus replication thereby enhancing cell survival.
Effect of MG-132 on myofibrillogenesis and the ubiquitination of GAPDH in quail myotubes
In the three-step myofibrillogenesis model, mature myofibrils are formed through two intermediate structures: premyofibrils and nascent myofibrils. We have recently reported that several inhibitors of the Ubiquitin Proteosome System, for example, MG-132, and DBeQ, reversibly block progression of nascent myofibrils to mature myofibrils. In this investigation, we studied the effects of MG132 and DBeQ on the expression of various myofibrillar proteins including actin, myosin light and heavy chains, tropomyosin, myomesin, and myosin binding protein-C in cultured embryonic quail myotubes by western blotting using two loading controls-α-tubulin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Surprisingly, we found that MG-132 affected the level of expression of GAPDH but DBeQ did not. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative reverse transcription-PCR (qRT-PCR) showed no significant effect of MG-132 on GAPDH transcription. Two-dimensional (2D) western blot analyses with extracts of control and MG-132-treated cells using anti-ubiquitin antibody indicated that MG132-treated myotubes show a stronger emitter-coupled logic signal. However, Spot% and Spot volume calculations for all spots from both western blot film signals and matched Coomassie-stained 2D polyacrylamide gel electrophoresis showed that the intensity of staining in a spot of ~39 kDa protein is 3.5-fold lower in the gel of MG-132-treated extracts. Mass spectrometry analyses identified the ~39 kDa protein as quail GAPDH. Immunohistochemical analysis of fixed MG-132-treated myotubes with anti-GAPDH antibody showed extensive clump formation, which may be analogous to granule formation by stress response factors in MG132-treated cells. This is the first report on in vivo ubiquitination of GAPDH. This may be essential for the moonlighting (Jeffery, 1999) activity of GAPDH for tailoring stress in myotubes.
MG-132 treatment promotes TRAIL-mediated apoptosis in SEB-1 sebocytes
Aims: This study aimed to identify the mechanism of how MG-132 stimulates cell death in SEB-1 sebocytes.
Materials and methods: TUNEL staining and annexin-FITC/PI flow cytometry were utilized to examine the apoptotic cell number of SEB-1 sebocytes and HaCaT keratinocytes upon MG-132 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment. MTT assay and CCK-8 assay monitored the proliferative rate and viability of both cell lines with different treatment. Western blotting (WB) and qPCR were performed to detect the expression of TRAIL and members of Bcl-2 family at protein and gene level. Additionally, RNA interfering was used to knockdown the mRNA transcription of TRAIL and BIK gene.
Key findings: MG-132 treatment enhanced cell death in SEB-1 sebocytes but not in HaCaT keratinocytes. Meanwhile, TRAIL concentrations in SEB-1 sebocytes treated with MG-132 were markedly elevated. Furthermore, treatment with TRAIL or the TRAIL receptor-specific monoclonal antibody AY4 at various doses stimulated cell death in SEB-1 sebocytes in a time- and dose-dependent manner. Silencing of TRAIL restored the cell viability of SEB-1 cells to a normal level after MG-132 treatment. Combined treatment of SEB-1 sebocytes with TRAIL and MG-132 synergistically triggered cell death, suppressed cell proliferation and survival, and promoted BIK expression. Furthermore, BCL2 Interacting Killer (BIK) knockdown via RNA interference participated in the recovery of cell survival reduced by treatment with TRAIL and MG-132.
Significance: These findings suggest that treatment with the selective proteasome suppressor MG-132 and TRAIL induces cell death in sebocytes through upregulation of BIK, a member of the Bcl-2 family.
MG-132 reduces virus release in Bovine herpesvirus-1 infection
Bovine herpesvirus 1 (BoHV-1) can provoke conjunctivitis, abortions and shipping fever. BoHV-1 infection can also cause immunosuppression and increased susceptibility to secondary bacterial infections, leading to pneumonia and occasionally to death. Herein, we investigated the influence of MG-132, a proteasome inhibitor, on BoHV-1 infection in bovine kidney (MDBK) cells. Infection of MDBK cells with BoHV-1 induces apoptotic cell death that enhances virus release. Whereas, MG-132 inhibited virus-induced apoptosis and stimulated autophagy. Protein expression of viral infected cell protein 0 (bICP0), which is constitutively expressed during infection and is able to stimulate Nuclear factor kappa B (NF-κB), was completely inhibited by MG-132. These results were accompanied by a significant delay in the NF-κB activation. Interestingly, the efficient virus release provoked by BoHV-1-induced apoptosis was significantly reduced by MG-132. Overall, this study suggests that MG-132, through the activation of autophagy, may limit BoHV-1 replication during productive infection, by providing an antiviral defense mechanism.