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https://www.readbyqxmd.com/read/29442024/anti-cancer-activity-of-bacillus-amyloliquefaciens-ak-0-through-cyclin-d1-proteasomal-degradation-via-gsk3%C3%AE-dependent-phosphorylation-of-threonine-286
#1
Gwang Hun Park, Hun Min Song, Young Soo Kim, Yongho Jeon, Jin Suk Koo, Hyung Jin Jeong, Jin Boo Jeong
Microorganisms have been regarded as important sources of novel bioactive natural products. In this study, we evaluated the anti-cancer activity and the potential mechanism of Bacillus amyloliquefaciens AK-0 newly isolated from the rhizosphere soil of Korean ginseng. The ethyl acetate fraction from the culture medium of B. amyloliquefaciens AK-0 (EA-AK0) inhibited markedly the proliferation of human colorectal cancer cells such as HCT116, SW480, LoVo and HT-29. EA-AK0 effectively decreased cyclin D1 protein level in human colorectal cancer cells, while cyclin D1 mRNA level was not changed by EA-AK0 treatment...
June 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29407955/discovery-of-a-keap1-dependent-peptide-protac-to-knockdown-tau-by-ubiquitination-proteasome-degradation-pathway
#2
Mengchen Lu, Tian Liu, Qiong Jiao, Jianai Ji, Mengmin Tao, Yijun Liu, Qidong You, Zhengyu Jiang
Induced protein degradation by PROTACs has emerged as a promising strategy to target nonenzymatic proteins inside the cell. The aim of this study was to identify Keap1, a substrate adaptor protein for ubiquitin E3 ligase involved in oxidative stress regulation, as a novel candidate for PROTACs that can be applied in the degradation of the nonenzymatic protein Tau. A peptide PROTAC by recruiting Keap1-Cul3 ubiquitin E3 ligase was developed and applied in the degradation of intracellular Tau. Peptide 1 showed strong in vitro binding with Keap1 and Tau...
February 1, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29399107/effect-of-prp105-132-on-the-secretion-of-interleukin-6-and-interleukin-8-from-microglial-cells-in-vitro
#3
Yun-Tian Yang, Shan Jin
In the present study, the effect of prion protein (PrP) on the secretion of interleukin-6 (IL-6) and IL-8 from microglial cells in vitro and its possible underlying pathway were investigating by establishing a cell model for prion disease. Rat neuroglial cells were cultured in vitro, and were treated with 80 µM PrP peptides 105-132 (PrP105-132) only, PrP+MG132 or PrP+cyclosporin A (CsA). After 48 h, the IL-6 and IL-8 levels in the supernatant fluid of the treated cells were detected using enzyme-linked immunosorbent assay...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29391579/a-missense-mutation-in-trappc6a-leads-to-build-up-of-the-protein-in-patients-with-a-neurodevelopmental-syndrome-and-dysmorphic-features
#4
Hussein Sheikh Mohamoud, Saleem Ahmed, Musharraf Jelani, Nuha Alrayes, Kay Childs, Nirmal Vadgama, Mona Mohammad Almramhi, Jumana Yousuf Al-Aama, Steve Goodbourn, Jamal Nasir
Childhood onset clinical syndromes involving intellectual disability and dysmorphic features, such as polydactyly, suggest common developmental pathways link seemingly unrelated phenotypes. We identified a consanguineous family of Saudi origin with varying complex features including intellectual disability, speech delay, facial dysmorphism and polydactyly. Combining, microarray based comparative genomic hybridisation (CGH) to identify regions of homozygosity, with exome sequencing, led to the identification of homozygous mutations in five candidate genes (RSPH6A, ANKK1, AMOTL1, ALKBH8, TRAPPC6A), all of which appear to be pathogenic as predicted by Proven, SIFT and PolyPhen2 and segregate perfectly with the disease phenotype...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29363325/short-term-high-glucose-treatment-decreased-abundance-of-orai1-protein-through-posttranslational-mechanisms-in-rat-mesangial-cells
#5
Hui Jiang, Shubiao Zou, Sarika Chaudhari, Rong Ma
The short-term effect of high glucose (HG) treatment on store-operated Ca2+ entry in mesangial cells (MCs) is not well known. The aim of the present study was to determine whether and how HG treatment for a short period altered protein abundance of Orai1, the channel mediating store-operated Ca2+ entry in MCs. Rat and human MCs were exposed to HG (25 mM) for 2, 4, 8, and 24 hours and the abundance of Orai1 protein was significantly decreased at the time point of 8 and 16 hours. Consistently, HG treatment for 8 hours significantly reduced store-operated Ca2+ entry in rat MCs...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29346283/the-biological-role-of-hyaluronan-rich-oocyte-cumulus-extracellular-matrix-in-female-reproduction
#6
REVIEW
Eva Nagyova
Fertilization of the mammalian oocyte requires interactions between spermatozoa and expanded cumulus extracellular matrix (ECM) that surrounds the oocyte. This review focuses on key molecules that play an important role in the formation of the cumulus ECM, generated by the oocyte-cumulus complex. In particular, the specific inhibitors (AG1478, lapatinib, indomethacin and MG132) and progesterone receptor antagonist (RU486) exerting their effects through the remodeling of the ECM of the cumulus cells surrounding the oocyte have been described...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29345424/a-fluorescence-based-sensor-assay-that-monitors-general-protein-aggregation-in-human-cells
#7
Marisa Pereira, Diogo Tomé, Ana S Domingues, Ana S Varanda, Cristiana Paulo, Manuel A S Santos, Ana R Soares
Protein conformational disorders are characterized by disruption of protein folding and toxic accumulation of protein aggregates. Here we describe a sensitive and simple method to follow and monitor general protein aggregation in human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock protein that binds and keeps unfolded proteins in a folding competent state. This high specificity of HSP27 for aggregated proteins can be explored to monitor aggregation in living cells by fusing it to a fluorescent protein as Green Fluorescent Protein (GFP)...
January 18, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29340644/proteasome-inhibition-increases-the-efficiency-of-lentiviral-vector-mediated-transduction-of-trabecular-meshwork
#8
Zeynep Aktas, Hongyu Rao, Sarah R Slauson, B'Ann T Gabelt, Inna V Larsen, Rachael T C Sheridan, Leonie Herrnberger, Ernst R Tamm, Paul L Kaufman, Curtis R Brandt
Purpose: To determine if proteasome inhibition using MG132 increased the efficiency of FIV vector-mediated transduction in human trabecular meshwork (TM)-1 cells and monkey organ-cultured anterior segments (MOCAS). Methods: TM-1 cells were pretreated for 1 hour with 0.5% dimethyl sulfoxide (DMSO; vehicle control) or 5 to 50 μM MG132 and transduced with FIV.GFP (green fluorescent protein)- or FIV.mCherry-expressing vector at a multiplicity of transduction (MOT) of 20...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29339435/corrected-and-republished-from-the-cop9-signalosome-interacts-with-and-regulates-interferon-regulatory-factor-5-protein-stability
#9
Justyna Korczeniewska, Betsy J Barnes
The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability...
February 1, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29332931/proteasome-inhibitor-carbobenzoxy-l-leucyl-l-leucyl-l-leucinal-mg132-enhances-therapeutic-effect-of-paclitaxel-on-breast-cancer-by-inhibiting-nuclear-factor-nf-%C3%AE%C2%BAb-signaling
#10
Yunjing Zhang, Bin Yang, Jinping Zhao, Xiaoli Li, Long Zhang, Zhenhua Zhai
BACKGROUND Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), a peptide aldehyde proteasome inhibitor, can inhibit tumor progression by inactivating nuclear factor (NF)-κB signaling. Paclitaxel (PTX) is part of a routine regimen for the treatment of breast cancer. However, activation of the NF-κB pathway after treatment with PTX confers insensitivity to this drug. This study investigated the potential effect of MG132 as a co-treatment with PTX against breast cancer, and clarifies the underlying molecular mechanisms...
January 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29330041/acute-epileptiform-activity-induced-by-gabazine-involves-proteasomal-rather-than-lysosomal-degradation-of-kca2-2-channels
#11
Steffen Müller, Xiati Guli, Judith Hey, Anne Einsle, Daniela Pfanz, Victor Sudmann, Timo Kirschstein, Rüdiger Köhling
Voltage-independent, Ca2+-activated K+ channels (KCa2.2, previously named SK2) are typically activated during a train of action potentials, and hence, are powerful regulators of cellular excitability by generating an afterhyperpolarizing potential (AHP) following prolonged excitation. In the acute in vitro epilepsy model induced in hippocampal brain slice preparations by exposure to the GABAA receptor blocker gabazine (GZ), the AHP was previously shown to be significantly decreased. Here, we asked the question whether KCa2...
January 9, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29277369/implication-of-altered-ubiquitin-proteasome-system-and-er-stress-in-the-muscle-atrophy-of-diabetic-rats
#12
S Sreenivasa Reddy, Karnam Shruthi, Y Konda Prabhakar, Gummadi Sailaja, G Bhanuprakash Reddy
BACKGROUND: Skeletal muscle is adversely affected in type-1 diabetes, and excessively stimulated ubiquitin-proteasome system (UPS) was found to be a leading cause of muscle wasting or atrophy. The role of endoplasmic reticulum (ER) stress in muscle atrophy of type-1 diabetes is not known. Hence, we investigated the role of UPS and ER stress in the muscle atrophy of chronic diabetes rat model. METHODS: Diabetes was induced with streptozotocin (STZ) in male Sprague-Dawley rats and were sacrificed 2- and 4-months thereafter to collect gastrocnemius muscle...
December 22, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29246658/aberrant-subcellular-localization-of-sqstm1-p62-contributes-to-increased-vulnerability-to-proteotoxic-stress-recovery-in-huntington-s-disease
#13
Ningjing Huang, Christine Erie, Michael L Lu, Jianning Wei
Proteotoxic stress plays an important role in the pathogenesis of Huntington's disease (HD). Autophagy is proposed as a compensatory mechanism to remove protein aggregates under proteotoxic stress by up-regulating p62 expression. In the present study, we investigated the molecular action of p62 to proteotoxic stress in HD cells. Using two different HD cellular models, STHdhQ7 and STHdhQ111 cells derived from wild type and HD knock-in mice and human fibroblasts from healthy and HD patients, we found that HD cells are more vulnerable to cell death under proteotoxic stress and during stress recovery...
December 12, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29225318/caffeine-stimulated-intestinal-epithelial-cells-suppress-lipid-accumulation-in-adipocytes
#14
Takakazu Mitani, Tomoya Nagano, Kiyonari Harada, Yoko Yamashita, Hitoshi Ashida
Caffeine is a methylxanthine derived from plant foods such as coffee beans and tea leaves, and has multiple biological activities against physiological response and several diseases. Although there are some reports about the direct effect of caffeine against anti-lipid accumulation in vitro, the effect of caffeine on lipid accumulation in adipocytes through stimulating intestinal epithelial cells is unknown. Since direct treatment with caffeine to 3T3-L1 cells did not affect lipid accumulation, we determined whether caffeine-stimulated intestinal epithelial Caco-2 cells influence the lipid accumulation in 3T3-L1 adipocytes...
2017: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/29212961/ubiquitin-proteasome-system-modulates-zygotic-genome-activation-in-early-mouse-embryos-and-influences-full-term-development
#15
Chika Higuchi, Natsumi Shimizu, Seung-Wook Shin, Kohtaro Morita, Kouhei Nagai, Masayuki Anzai, Hiromi Kato, Tasuku Mitani, Kazuo Yamagata, Yoshihiko Hosoi, Kei Miyamoto, Kazuya Matsumoto
Maternal RNA/protein degradation and zygotic genome activation (ZGA), occurring during maternal-to-zygotic transition (MZT), are the first essential events for the development of pre-implantation embryos. Previously, we have shown the importance of the ubiquitin-proteasome system (UPS) for initiation of minor ZGA at the 1-cell stage of mouse embryos. However, little is known about the mechanism of involvement of the UPS-degraded maternal proteins in ZGA. In this study, we investigated the effect of inhibiting maternal protein degradation by the reversible proteasome inhibitor, MG132, on post-implantation development and ZGA regulation during early cleavage stages...
December 7, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29205851/regulated-cell-death-of-lymphoma-cells-after-graded-mitochondrial-damage-is-differentially-affected-by-drugs-targeting-cell-stress-responses
#16
Tomás Lombardo, Martín Gil Folgar, Luciana Salaverry, Estela Rey-Roldán, Elida M Alvarez, María C Carreras, Laura Kornblihtt, Guillermo A Blanco
Collapse of the mitochondrial membrane potential (MMP) is often considered the initiation of regulated cell death (RCD). Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) is an uncoupler of the electron transport chain (ETC) that facilitates the translocation of protons into the mitochondrial matrix leading to the collapse of the MMP. Several cell stress responses such as mitophagy, mitochondrial biogenesis and the ubiquitin proteasome system, may differentially contribute to restrain the initiation of RCD depending on the extent of mitochondrial damage...
December 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29196261/a-674563-increases-chondrocyte-marker-expression-in-cultured-chondrocytes-by-inhibiting-sox9-degradation
#17
Tomohito Kobayashi, Kaori Fujita, Takashi Kamatani, Shuichi Matsuda, Noriyuki Tsumaki
The implantation of autologous chondrocytes is a therapeutic treatment for articular cartilage damage. However, the benefits are limited due to the expansion of chondrocytes in monolayer culture, which causes loss of chondrocytic characters. Therefore, culture conditions that enhance chondrocytic characters are needed. We screened 5822 compounds and found that A-674563 enhanced the transcription of several chondrocyte marker genes, including Col2a1, Acan and Col11a2, in mouse primary chondrocytes. Experiments using cycloheximide, MG132 and bafilomycin A1 have revealed that Sox9 is degraded through the ubiquitin-proteasome pathway and that A-674563 inhibits this degradation, resulting in larger amount of Sox9 protein...
November 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29191827/proteasome-mediated-degradation-of-collagen-iii-by-cortisol-in-amnion-fibroblasts
#18
Yabing Mi, Wangsheng Wang, Jiangwen Lu, Chuyue Zhang, Yawei Wang, Hao Ying, Kang Sun
Rupture of fetal membranes (ROM) can initiate parturition at both term and preterm. Collagen III in the compact layer of the amnion contributes to the tensile strength of fetal membranes. However, the upstream signals triggering collagen III degradation remain mostly elusive. In this study we investigated the role of cortisol regenerated by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in collagen III degradation in human amnion fibroblasts with an aim to seek novel targets for the prevention of preterm premature ROM (PPROM)-elicited preterm birth...
November 30, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29191257/proteasome-inhibitor-mg132-enhances-cisplatin-induced-apoptosis-in-osteosarcoma-cells-and-inhibits-tumor-growth
#19
Farui Sun, Yuanjin Zhang, Lijun Xu, Songbai Li, Xiang Chen, Ling Zhang, Yifan Wu, Jun Li
Although cisplatin has been proved as an integral part of chemotherapy regiment in osteosarcoma (OS) treatment, toxicity issues and chemoresistance hindered the OS therapeutic development. Exploring novel combination therapy methods is required to circumvent the limitations of cisplatin alone. The proteasome inhibitor MG132 has shown its anti-tumor effects in many solid tumors. However, little is known about its effects in combination with cisplatin in osteosarcoma cells. In this study, we examined the effects of MG132 in combination with cisplatin in human osteosarcoma cells (MG-63 and HOS)...
November 30, 2017: Oncology Research
https://www.readbyqxmd.com/read/29184507/kir2-1-nav1-5-channel-complexes-are-differently-regulated-than-kir2-1-and-nav1-5-channels-alone
#20
Raquel G Utrilla, Paloma Nieto-Marín, Silvia Alfayate, David Tinaquero, Marcos Matamoros, Marta Pérez-Hernández, Sandra Sacristán, Lorena Ondo, Raquel de Andrés, F Javier Díez-Guerra, Juan Tamargo, Eva Delpón, Ricardo Caballero
Cardiac Kir2.1 and Nav1.5 channels generate the inward rectifier K+ (IK1) and the Na+ (INa) currents, respectively. There is a mutual interplay between the ventricular INa and IK1 densities, because Nav1.5 and Kir2.1 channels exhibit positive reciprocal modulation. Here we compared some of the biological properties of Nav1.5 and Kir2.1 channels when they are expressed together or separately to get further insights regarding their putative interaction. First we demonstrated by proximity ligation assays (PLAs) that in the membrane of ventricular myocytes Nav1...
2017: Frontiers in Physiology
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