Search results for: Caspase Family Inhibitor Set
#28960945 2017/09/29 Save this To Up
Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells.Malignant pleural mesothelioma (MPM), an asbestos-related occupational disease, is an aggressive and incurable tumor of the thoracic cavity. Despite recent advances in MPM treatment, overall survival of patients with MPM is very low. Recent studies have implicated that PI3K/Akt signaling is involved in MPM cell survival and development. To investigate the effects of Akt inhibitors on MPM cell survival, we examined the effects of nine selective Akt inhibitors, namely, afuresertib, Akti-1/2, AZD5363, GSK690693, ipatasertib, MK-2206, perifosine, PHT-427, and TIC10, on six MPM cell lines, namely, ACC-MESO-4, Y-MESO-8A, MSTO-211H, NCI-H28, NCI-H290, and NCI-H2052, and a normal mesothelial cell line MeT-5A. Comparison of IC50 values of the Akt inhibitors showed that afuresertib, an ATP-competitive specific Akt inhibitor, exerted tumor-specific effects on MPM cells. Afuresertib significantly increased caspase-3 and caspase-7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Moreover, afuresertib strongly arrested the cell cycle in the G1 phase. Western blotting analysis showed that afuresertib increased the expression of p21(WAF)(1/)(CIP)(1) and decreased the phosphorylation of Akt substrates, including GSK-3β and FOXO family proteins. These results suggest that afuresertib-induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Furthermore, afuresertib significantly enhanced cisplatin-induced cytotoxicity. Interestingly, results of gene set enrichment analysis showed that afuresertib modulated the expression E2F1 and MYC, which are associated with fibroblast core serum response. Together, these results suggest that afuresertib is a useful anticancer drug for treating patients with MPM.
2916 related Products with: Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells.Epidermal Growth Factor ( Epidermal Growth Factor ( Akt Inhibitor1 mg Akt Inhibitor, Isozyme Se Glucagon ELISA KIT, Rat G AZD-5363 Mechanisms: Akt GDC-0068 Mechanisms: Akt PathwayReady™ PI3 K Akt D Luciferin, 6' methyl et MarkerGeneTM Gaussia Luci Tissue array of ovarian g Fontana-Masson Stain Kit
#28040362 2017/01/01 Save this To Up
Role of the NLRP3 inflammasome in a model of acute burn-induced pain.The NLRP3 inflammasome is a multi-protein complex that assembles in response to tissue damage or infection, triggering activation of caspase-1, an enzyme that converts interleukin (IL)-1β into its active form. A role for the NLRP3 inflammasome is emerging in inflammatory pain, but its influence in other pain types is largely unexamined. Therefore the aim of this study was to assess the role of the NLRP3 inflammasome and its downstream product caspase-1 in a model of acute burn-induced pain in male mice. A superficial burn was induced on the plantar surface of the left hind paw using a hot plate set at 52.5°C for 25s. Development of burn-induced mechanical allodynia, thermal allodynia, edema and weight bearing changes was assessed in Nlrp3(-/-) and caspase-1-deficient (Ice(-/-)) mice, and in mice administered the selective NLRP3 inflammasome inhibitor MCC950. Burn-induced mechanical and thermal allodynia developed normally in Nlrp3(-/-) and Ice(-/-) mice and mice administered MCC950. Burn-induced edema was significantly reduced in Ice(-/-) mice only. Burn-induced weight bearing changes were attenuated in Nlrp3(-/-) mice and mice administered MCC950 72h after burn only. This study suggests that NLRP3 and its downstream product caspase-1 have a limited role in the development of burn-induced pain.
Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon TGF beta induced factor 2 Anti beta3 AR Human, Poly Thermal Shaker with cooli FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu
#26566079 2016/02/05 Save this To Up
Pharmacodynamic markers and clinical results from the phase 2 study of the SMAC mimetic birinapant in women with relapsed platinum-resistant or -refractory epithelial ovarian cancer.Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. It was hypothesized that blocking IAPs with birinapant would increase tumor cell death and result in objective responses for women with platinum-refractory and -resistant ovarian cancer.
2479 related Products with: Pharmacodynamic markers and clinical results from the phase 2 study of the SMAC mimetic birinapant in women with relapsed platinum-resistant or -refractory epithelial ovarian cancer.Breast cancer tissue arra Multiple organ tumor tiss Ovarian cancer tissue arr Endocrine organ cancer te Ovarian cancer test tissu Oral cavity cancer test t Multi organ carcinoma tis Multi organ carcinoma tis Multiple organ cancer tis Colon cancer and normal t Prostate cancer, adjacent Bladder cancer tissue arr
#26462035 2016/02/24 Save this To Up
Inhibitor of apoptosis proteins as intracellular signaling intermediates.Inhibitor of apoptosis (IAP) proteins have often been considered inhibitors of cell death due to early reports that described their ability to directly bind and inhibit caspases, the primary factors that implement apoptosis. However, a greater understanding is evolving regarding the vital roles played by IAPs as transduction intermediates in a diverse set of signaling cascades associated with functions ranging from the innate immune response to cell migration to cell-cycle regulation. In this review, we discuss the functions of IAPs in signaling, focusing primarily on the cellular IAP (c-IAP) proteins. The c-IAPs are important components in tumor necrosis factor receptor superfamily signaling cascades, which include activation of the NF-κB transcription factor family. As these receptors modulate cell proliferation and cell death, the involvement of the c-IAPs in these pathways provides an additional means of controlling cellular fate beyond simply inhibiting caspase activity. Additionally, IAP-binding proteins, such as Smac and caspases, which have been described as having cell death-independent roles, may affect c-IAP activity in intracellular signaling. Collectively, the multi-faceted functions and complex regulation of the c-IAPs illustrate their importance as intracellular signaling intermediates.
1055 related Products with: Inhibitor of apoptosis proteins as intracellular signaling intermediates.EMAP-II Inhibitor Z-ASTD- EMAP-II Inhibitor Z-ASTD- EMAP II Inhibitor Z ASTD EMAP II Inhibitor Z ASTD Amplite™ Intracellular Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Caspase 3 7 Cell Meter™ Caspase 3 7
#26104676 2015/06/30 Save this To Up
Age-related increases in amyloid beta and membrane attack complex: evidence of inflammasome activation in the rodent eye.The membrane attack complex (MAC) is a key player in the pathogenesis of age-related macular degeneration (AMD) and is a putative activator of the NLRP3 inflammasome. Amyloid beta (Aβ), a component of drusen deposits, has also been implicated in inflammasome activation by our work and those of others. However, the interactions of MAC and Aβ are still poorly understood, especially their roles in aging and retinal degenerative pathologies. Since inflammasome activation may represent a key cellular pathway underlying age-related chronic inflammation in the eye, the purpose of this study is to identify the effects associated with MAC and inflammasome activation in the retinal pigment epithelium (RPE)/choroid and to evaluate the therapeutic merits of MAC suppression.
2173 related Products with: Age-related increases in amyloid beta and membrane attack complex: evidence of inflammasome activation in the rodent eye.Beta Amyloid (42) ELISA K Beta Amyloid (1 40) ELISA Beta Amyloid (40) ELISA K Beta Amyloid (1 40) ELISA Nuclear Membrane Receptor to FAPβ (Fibroblast Act to FAPβ (Fibroblast Act Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Human Macrophage Inflamma
#25700738 2015/02/21 Save this To Up
Mitochondrial damage contributes to Pseudomonas aeruginosa activation of the inflammasome and is downregulated by autophagy.The nucleotide-binding domain, leucine-rich repeat containing family caspase recruitment domain containing 4 (NLRC4) inflammasome can be activated by pathogenic bacteria via products translocated through the microbial type III secretion apparatus (T3SS). Recent work has shown that activation of the NLRP3 inflammasome is downregulated by autophagy, but the influence of autophagy on NLRC4 activation is unclear. We set out to determine how autophagy might influence this process, using the bacterium Pseudomonas aeruginosa, which activates the NLRC4 inflammasome via its T3SS. Infection resulted in T3SS-dependent mitochondrial damage with increased production of reactive oxygen intermediates and release of mitochondrial DNA. Inhibiting mitochondrial reactive oxygen release or degrading intracellular mitochondrial DNA abrogated NLRC4 inflammasome activation. Moreover, macrophages lacking mitochondria failed to activate NLRC4 following infection. Removal of damaged mitochondria by autophagy significantly attenuated NLRC4 inflammasome activation. Mitochondrial DNA bound specifically to NLRC4 immunoprecipitates and transfection of mitochondrial DNA directly activated the NLRC4 inflammasome; oxidation of the DNA enhanced this effect. Manipulation of autophagy altered the degree of inflammasome activation and inflammation in an in vivo model of P. aeruginosa infection. Our results reveal a novel mechanism contributing to NLRC4 activation by P. aeruginosa via mitochondrial damage and release of mitochondrial DNA triggered by the bacterial T3SS that is downregulated by autophagy.
2190 related Products with: Mitochondrial damage contributes to Pseudomonas aeruginosa activation of the inflammasome and is downregulated by autophagy.BACTERIOLOGY PSEUDOMONAS PSEUDOMONAS AERUGINOSA cl Mouse Anti P. aeruginosa Mouse Anti P.aeruginosa s Mouse Anti P.aeruginosa s Shiga Toxin 1 antibody, M Shiga Toxin 2 antibody, M Cholera toxin antibody, M Clostridium botulinum D T Clostridum difficile toxi Clostridum difficile toxi Clostridum difficile toxi
#24960127 2014/06/25 Save this To Up
tLivin displays flexibility by promoting alternative cell death mechanisms.Livin is a member of the Inhibitor of Apoptosis (IAP) protein family that inhibits apoptosis triggered by a variety of stimuli. We previously demonstrated that while Livin inhibits caspase activity, caspases can cleave Livin to produce a truncated protein, tLivin and that this newly formed tLivin paradoxically induces cell death. However to date, the mechanism of tLivin-induced cell death is not fully understood. In this study, we set out to characterize the form of cell death mediated by tLivin. Here we demonstrate that, unlike most death-promoting proteins, tLivin is a flexible inducer of cell death capable of promoting necrosis or apoptosis in different cell lines. The unusual flexibility of tLivin is displayed by its ability to activate an alternative form of cell death when apoptosis is inhibited. Thus, tLivin can promote more than one form of cell death in the same cell type. Interestingly, in cells where tLivin induces necrosis, deletion of the caspase binding BIR domain results in tLivin-induced apoptosis, suggesting the BIR domain can potentially hamper the ability of tLivin to induce apoptosis. We further elucidate that tLivin activates the JNK pathway and both tLivin-induced apoptosis and necrosis are partially mediated by JNK activity. Acquired resistance to apoptosis, common in many tumors, impinges on the efficiency of conventional anti-cancer agents that function primarily by inducing apoptosis. The ability of tLivin to induce death of apoptosis-compromised cells makes it an attractive candidate for targeted cancer therapy.
1526 related Products with: tLivin displays flexibility by promoting alternative cell death mechanisms.BYL-719 Mechanisms: PI3K- Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in Rabbit Anti-Cell death in
#24658911 2015/01/02 Save this To Up
B7-H4 downregulation induces mitochondrial dysfunction and enhances doxorubicin sensitivity via the cAMP/CREB/PGC1-α signaling pathway in HeLa cells.B7-H4 is a B7 family coregulatory protein that inhibits T cell-mediated immunity. B7-H4 is overexpressed in various cancers; however, the functional role of B7-H4 in cancer metabolism is poorly understood. Because mitochondria play pivotal roles in development, proliferation, and death of cancer cells, we investigated molecular and functional alterations of mitochondria in B7-H4-depleted HeLa cells. In a human study, overexpression of B7-H4 was confirmed in the cervices of adenocarcinoma patients (n = 3) compared to noncancer patients (n = 3). In the cell line model, B7-H4 depletion was performed by transfection with small interfering RNA (siRNA). B7-H4 depletion suppressed oxygen consumption rate, ATP production, and mitochondrial membrane potential and mass and increased reactive oxygen species production. In particular, electron transport complex III activity was significantly impaired in siB7-H4-treated cells. Coincidently, depletion of B7-H4 suppressed major mitochondrial regulators (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC1-α] and mitochondrial transcription factor A), a component of oxidative phosphorylation (ubiquinol-cytochrome c reductase core protein 1), and an antiapoptosis protein (Bcl-XL). Mitochondrial dysfunction in siRNA-treated cells significantly augmented oxidative stress, which strongly activated the JNK/P38/caspase axis in the presence of doxorubicin, resulting in increased apoptotic cell death. Investigating the mechanism of B7-H4-mediated mitochondrial modulation, we found that B7-H4 depletion significantly downregulated the cAMP/cAMP response element-binding protein/PGC1-α signaling pathway. Based on these findings, we conclude that B7-H4 has a role in the regulation of mitochondrial function, which is closely related to cancer cell physiology and drug sensitivity.
2414 related Products with: B7-H4 downregulation induces mitochondrial dysfunction and enhances doxorubicin sensitivity via the cAMP/CREB/PGC1-α signaling pathway in HeLa cells.AP-1 Reporter – HEK293 Wnt Signaling Pathway TCF AKT PKB Signaling Phospho AMPK Signaling Phospho-Sp CREB Phospho-Specific Arr ErbB Her Signaling Phosph ERK Signaling Phospho-Spe GPCR Signaling to MAPK ER IGF-1R Signaling Phospho- NF-kB II Phospho-Specific p53 Signaling Phospho-Spe T-Cell Receptor Signaling
#24291026 2014/01/13 Save this To Up
Array CGH analysis of a cohort of Russian patients with intellectual disability.The use of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated the identification of many new microdeletion/microduplication syndromes (MMSs). Furthermore, this method has allowed for the identification of copy number variations (CNVs) whose pathogenic role has yet to be uncovered. Here, we report on our application of array CGH for the identification of pathogenic CNVs in 79 Russian children with intellectual disability (ID). Twenty-six pathogenic or likely pathogenic changes in copy number were detected in 22 patients (28%): 8 CNVs corresponded to known MMSs, and 17 were not associated with previously described syndromes. In this report, we describe our findings and comment on genes potentially associated with ID that are located within the CNV regions.
1024 related Products with: Array CGH analysis of a cohort of Russian patients with intellectual disability.Analysis Tool for AAM-BLG Analysis Tool for AAM-BLM Analysis Tool for AAM-ISO Analysis Tool for AAR-BLG Analysis Tool for AAR-BLM Analysis Tool for Custom Analysis Tool for Custom Analysis Tool for AAH-ADI Analysis Tool for AAH-ADI Analysis Tool for AAH-AKI Analysis Tool for AAH-AKI Analysis Tool for AAH-ANG
#24036212 2013/10/21 Save this To Up
Activation of integrin β1-focal adhesion kinase-RasGTP pathway plays a critical role in TGF beta1-induced podocyte injury.The depletion of glomerular podocytes is the key mechanism of glomerulosclerosis and progressive renal failure. Transforming growth factor-β (TGFβ) is a central mediator of signaling networks that control a diverse set of cellular processes, such as cell proliferation, differentiation, and apoptosis. Though many key events in TGFβ1 signaling have been documented at cellular and molecular level in podocytes, the complete effects of TGFβ1 on podocyte integrity are still elusive. In this study, the function of adhesion protein integrin β1, focal adhesion kinase (FAK), and a small GTPase Ras was explored in TGFβ1-induced podocyte injury. In cultured mouse podocyte, caspase 3-positive cells were counted by flow cytometry to evaluate podocyte damage at different time points after TGFβ1 treatment. Immunoblotting assay showed that integrin β1, FAK, Src kinase, and an adaptor protein Grb2 were activated rapidly after TGFβ1 stimulation. Active Ras Pull-Down assay revealed that the active Ras (GTP-bound Ras) level was upregulated in TGFβ1-treated cell. Immunoprecipitation results displayed that TGFβ1 enhanced the complex formation of integrin β1, FAK and Src kinase, as well as FAK, Grb2 and Ras. The FAK inhibitor TAE226 and the specific knockdown of Grb2 remarkably alleviated TGFβ1-induced podocyte apoptosis. The activation of p38MAPK and Erk1/2, and the nuclear translocation of NFκB(p65) were increased evidently in TGFβ1-treated cell, which could be dramatically prohibited by the application of the p38MAPK inhibitor SB202190 and the Ras inhibitor FPT Inhibitor III. The Src kinase inhibitor PP2 obviously prevented the activation of FAK and Ras, as well as the translocation of NFκB(p65) from cytoplasm to nuclei. The PP2, FPT Inhibitor III, and SB202190 significantly decreased TGFβ1-induced podocyte apoptosis. Taken together, these data demonstrated that the activation of integrin β1/Src/FAK and Grb2/RasGTP should be responsible for TGFβ1-induced podocyte damage through the p38MAPK and Erk1/2-mediated nuclear translocation of NFκB(p65).
1778 related Products with: Activation of integrin β1-focal adhesion kinase-RasGTP pathway plays a critical role in TGF beta1-induced podocyte injury.Integrin β1 (CD29) Antib TGF beta induced factor 2 Anti beta3 AR Human, Poly TGF-Beta Signaling Phosph Anti-AICDA(Activation-ind Anti AICDA(Activation ind Anti VGLUT 1 Rat, polyclo Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Human, Monoclon Anti Rat VGLUT 2, Rabbit Anti AGO2 Mouse, Monoclon
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45 Fax 0032 16 50 90 45
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50 Fax 01 43 25 01 60
52062 Aachen Deutschland
Tel 0241 40 08 90 86 Fax 0241 55 91 05 36
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
Schweiz Züri +41435006251
Česká republika Praha +420246019719
Ireland Dublin +35316526556
Norge Oslo +4721031366
Finland Helsset +358942419041
Sverige Stockholm +46852503438
Ελλάς Αθήνα +302111768494
Magyarország Budapest +3619980547
GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
Tel 058 710 33 44
Fax 058 710 33 48
GENTAUR Nederland BV
5521 DG Eersel Nederland
Tel 0208-080893 Fax 0497-517897
Piazza Giacomo Matteotti, 6, 24122 Bergamo
Tel 02 36 00 65 93 Fax 02 36 00 65 94
53 Iskar Str. 1191 Kokalyane, Sofia