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20S proteasome

D Toliczenko-Bernatowicz, E Matuszczak, M Tylicka, A Sankiewicz, M Komarowska, E Gorodkiewicz, W Debek, A Hermanowicz
PURPOSE: To evaluate the concentration of 20S proteasome in the blood plasma of boys with cryptorchidism. METHODS: Patients-50 boys aged 1-4 years (median = 2.4 years) with unilateral cryptorchidism. The control group-50 healthy, age-matched boys (aged 1-4 years, median = 2.1 years), admitted for planned herniotomy. In our study, we used a novel technique Surface PLASMON RESONANCE Imaging. RESULTS: The median concentration of 20S proteasome in the blood plasma of boys with cryptorchidism was 2...
February 15, 2018: Journal of Endocrinological Investigation
Kuixiang Chen, Mubarak Rekep, Wei Wei, Qian Wu, Qin Xue, Sujuan Li, Jiahui Tian, Quan Yi, Genshui Zhang, Guiping Zhang, Qing Xiao, Jiandong Luo, Yinghua Liu
PURPOSE: Quercetin, a flavonoid, has been reported to ameliorate cardiovascular diseases, such as cardiac hypertrophy. However, the mechanism is not completely understood. In this study, a mechanism related to proteasome-glycogen synthesis kinase 3 (GSK-3) was elucidated in rats and primary neonatal cardiomyocytes. METHODS: Rats were subjected to sham or constriction of abdominal aorta surgery groups and treated with or without quercetin for 8 weeks. Angiotensin II (Ang II)-induced primary cardiomyocytes were cultured with quercetin treatment or not for 48 h...
February 12, 2018: Cardiovascular Drugs and Therapy
Hongwu Liu, Jianwei Wu, Ying Ge, Aibo Li, Jia Li, Zhengshi Liu, Yungen Xu, Qingxiang Xu, Yuyan Li
A novel series of non-peptide proteasome inhibitors (PIs) that act on chymotrypsin-like (ChT-L) of the proteasome were developed. These PIs bearing 4-aromatic sulfonyl naphthalene-based scaffold and Leu-boronic moiety as covalent bonding group displayed far better activity than PI-8182 for inhibiting ChT-L in preliminary biological activity test. The results showed that 2a (IC50 = 6.942 μM, MCF-7) and 2c (IC50 = 6.905 μM, MCF-7) displayed higher anti-proliferative activities than Bortezomib (IC50 = 18...
February 6, 2018: Bioorganic & Medicinal Chemistry
Yu-Chen Cheng, Wen-Chiuan Tsai, Yu-Chi Sung, Hsin-Han Chang, Ying Chen
BACKGROUND/AIMS: Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis. Proteasome subunit beta type-4 (PSMB4) is an essential subunit that contributes to the assembly of the 20S proteasome complex. However, the role of PSMB4 in glioblastomas remains to be clarified. The aim of this study was to investigate the role of PSMB4 in GBM tumor progression. METHODS: We first analyzed the PSMB4 protein and mRNA expression in 80 clinical brain specimens and 77 datasets from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database...
January 31, 2018: Cellular Physiology and Biochemistry
Makoto Tanaka, Yunhao Zhu, Masafumi Shionyu, Nozomi Ota, Natsumi Shibata, Chihiro Watanabe, Akihito Mizusawa, Ryuzo Sasaki, Tamio Mizukami, Isamu Shiina, Makoto Hasegawa
Ridaifen-F (RID-F) potently inhibits proteolytic activities of the 20S proteasome but poorly inhibits those of the 26S proteasome. Here, we report preparation of several conjugates in which various peptides are connected to RID-F. Conjugates with peptides consisting of seven amino acid residues significantly inhibited the 26S proteasome. Particularly, RID-F conjugated to an octaarginine peptide (R8, a so-called cell-penetrating peptide) inhibited intracellular proteasome activities and induced cell death in drug-resistant KMS-11 myeloma cells...
January 31, 2018: European Journal of Medicinal Chemistry
Fraser E Houston, Brian A Hain, Stephen L Dodd
Botulinum neurotoxin type A (BoNT/A) is used as a therapeutic tool to induce chemical denervation of spastically contracted muscles, yet the neurotoxin can also cause skeletal muscle atrophy. The underlying proteolytic mechanisms that induce this atrophy remain unclear. Our previous work has highlighted increased ubiquitin proteasome system (UPS) activity in soleus muscle of male Sprague Dawley rats following hind limb injection of BoNT/A, with the chymotrypsin-like activity of the 20s proteasome the most active...
February 3, 2018: Toxicon: Official Journal of the International Society on Toxinology
Miriam Kolog Gulko, Gabriele Heinrich, Carina Gross, Blagovesta Popova, Oliver Valerius, Piotr Neumann, Ralf Ficner, Gerhard H Braus
The transition from vegetative growth to multicellular development represents an evolutionary hallmark linked to an oxidative stress signal and controlled protein degradation. We identified the Sem1 proteasome subunit, which connects stress response and cellular differentiation. The sem1 gene encodes the fungal counterpart of the human Sem1 proteasome lid subunit and is essential for fungal cell differentiation and development. A sem1 deletion strain of the filamentous fungus Aspergillus nidulans is able to grow vegetatively and expresses an elevated degree of 20S proteasomes with multiplied ATP-independent catalytic activity compared to wildtype...
February 5, 2018: PLoS Genetics
Tyler A Wilson, Robert J Tokarski, Peter Sullivan, Robert M Demoret, Jimmy Orjala, L Harinantenaina Rakotondraibe, James R Fuchs
The human 20S proteasome inhibitor scytonemide A (1), a macrocyclic imine originally isolated from the cyanobacterium Scytonema hofmanni, was synthesized via a biomimetic solid-phase peptide synthesis (SPPS) approach employing the Weinreb AM resin. Utilizing this approach, cyclization of the protected heptapeptide via formation of the imine bond occurred spontaneously upon cleavage from the resin in the presence of a reducing agent and subsequent aqueous workup. The final deprotection step necessary to produce the natural product was accomplished under slightly basic conditions, facilitating cleavage of the silyl ether group while leaving the macrocycle intact...
February 5, 2018: Journal of Natural Products
Abdulsamie Hanano, Ibrahem Almousally, Mouhnad Shaban, Denis J Murphy
We have investigated the effects of dioxins on seed development in Arabidopsis thaliana. Dioxins are highly toxic persistent organic pollutants bioaccumulated by both plants and animals that also cause severe developmental abnormalities in humans. Plants were exposed to various concentrations of the most toxic congener of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the effects on seed development were analysed in depth at transcriptome, proteome and metabolome levels. Exposure to dioxin led to generalised effects on vegetative tissues plus a specific set of perturbations to seed development...
January 31, 2018: Journal of Experimental Botany
S M Curry, E R Burrough, K J Schwartz, K J Yoon, S M Lonergan, N K Gabler
Porcine epidemic diarrhea virus (PEDV) infects enterocytes and in nursery pigs, results in diarrhea, anorexia, and reduced performance. Therefore, the objective of this study was to determine how PEDV infection influenced growth performance and repartitioning of amino acids and energy in nursery pigs. A total of 32 barrows and gilts, approximately 1 week post-wean (BW = 8.46 ± 0.50 kg) and naïve for PEDV were obtained, weighed, and allotted based on sex and BW to 1 of 2 treatments: 1) Control, PEDV naïve and 2) PEDV-inoculated (PEDV) with 8 pens of 2 pigs each per treatment...
January 25, 2018: Journal of Animal Science
Michal Zigo, Karl Kerns, Miriam Sutovsky, Peter Sutovsky
Protein ubiquitination is a stable, reversible post-translational modification, targeting proteins for degradation/recycling by the 26S proteasome in a well-characterized enzymatic cascade. Studies have revealed the role of UPS in the regulation of fertilization, including sperm-zona pellucida interactions and the early event of sperm capacitation. The present study investigates the changes in proteasome compartmentalization, subunit composition and post-translational modifications during in vitro capacitation of fresh boar spermatozoa...
January 29, 2018: Cell and Tissue Research
Jiayi Huang, Jian L Campian, Amit D Gujar, Christina Tsien, George Ansstas, David D Tran, Todd A DeWees, A Craig Lockhart, Albert H Kim
Disulfiram has shown promising activity including proteasome inhibitory properties and synergy with temozolomide in preclinical glioblastoma (GBM) models. In a phase I study for newly diagnosed GBM after chemoradiotherapy, we have previously reported our initial dose-escalation results combining disulfiram with adjuvant temozolomide and established the maximum tolerated dose (MTD) as 500 mg per day. Here we report the final results of the phase I study including an additional dose-expansion cohort of disulfiram with concurrent copper...
January 27, 2018: Journal of Neuro-oncology
Kristin M O'Brien, Elizabeth L Crockett, Jacques Philip, Corey A Oldham, Megan Hoffman, Donald E Kuhn, Ronald Barry, Jessica McLaughlin
The unusual pattern of expression of hemoglobin (Hb) and myoglobin (Mb) among Antarctic notothenioid fishes provides an exceptional model system for assessing the impact of these proteins on oxidative stress. We tested the hypothesis that the lack of oxygen-binding proteins may reduce oxidative stress. Levels and activity of pro-oxidants, small-molecule and enzymatic antioxidants, and levels of oxidized lipids and proteins in liver, oxidative skeletal muscle, and heart ventricle were quantified in five species of notothenioid fishes differing in the expression of Hb and Mb...
December 21, 2017: Journal of Experimental Biology
Marie-Theres Vielberg, Verena C Bauer, Michael Groll
The 20S proteasome is a key player in eukaryotic and archaeal protein degradation, but its progenitor in eubacteria is unknown. Recently, the ancestral β-subunit protein (Anbu) was predicted to be the evolutionary precursor of the proteasome. We crystallised Anbu from Hyphomicrobium sp. strain MC1 in four different space groups and solved the structures by SAD-phasing and Patterson search calculation techniques. Our data reveal that Anbu adopts the classical fold of Ntn-hydrolases, but its oligomeric state differs from that of barrel-shaped proteases...
January 17, 2018: Journal of Molecular Biology
Evan DeVallance, Kayla W Branyan, Kent Lemaster, I Mark Olfert, David M Smith, Emidio E Pistilli, Jefferson C Frisbee, Paul D Chantler
AIMS: Perivascular adipose tissue (PVAT) is recognized for its vaso-active effects, however it's unclear how Metabolic Syndrome impact thoracic-aorta (t)PVAT and the subsequent effect on functional and structural aortic stiffness. METHODS & RESULTS: Thoracic aorta and tPVAT were removed from 16-17 week old lean (LZR, n = 16) and obese Zucker (OZR, n = 16) rats. OZR presented with aortic endothelial dysfunction, assessed by wire-myography, and increased aortic stiffness, assessed by elastic modulus...
January 18, 2018: Experimental Physiology
Nicolas Richy, Daad Sarraf, Xavier Maréchal, Naëla Janmamode, Rémy Le Guével, Emilie Genin, Michèle Reboud-Ravaux, Joëlle Vidal
Starting from the X-ray structure of our previous tripeptidic linear mimics of TMC-95A in complex with yeast 20S proteasome, we introduced new structural features to induce a differential inhibition between human constitutive and immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl alanine residues from tryptophan and their incorporation in peptides were described. Several potent inhibitors of human constitutive proteasome and immunoproteasome acting at the nanomolar level (IC50 = 7...
January 8, 2018: European Journal of Medicinal Chemistry
Xiaochuan Ma, Sangyun Lee, Xingshu Fei, Ge Fang, Tien Huynh, Yu Chong, Zhifang Chai, Cuicui Ge, Ruhong Zhou
Due to its hydrophobicity and other unique physicochemical properties, graphene oxide (GO) has been extensively utilized in various biological applications. However, introducing nanomaterials into the biological environment may raise serious risk in terms of nanotoxicity, leading to some unintended changes to the structure and the function of other biomolecules. This study investigates the interaction of GO with the ubiquitin-proteasome system, one of the essential machineries in the cellular metabolism, using a combination of experimental and computational approaches...
January 16, 2018: Nanotoxicology
Tilman Grune, Richard Kehm, Annika Höhn, Tobias Jung
Large amounts of data from multi-channel, high resolution, fluorescence microscopic images require tools that provide easy, customizable and reproducible high-throughput analysis. The freeware "ImageJ" has become one of the standard tools for scientific image analysis. Since ImageJ offers recording of "macros", even a complex multi-step process can be easily applied fully automated to large numbers of images, saving both time and reducing human subjective evaluation. In this work, we present "Cyt/Nuc", an ImageJ macro, able to recognize and to compare the nuclear and cytosolic areas of tissue samples, in order to investigate distributions of immunostained proteins between both compartments, while it documents in detail the whole process of evaluation and pattern recognition...
January 10, 2018: Biotechnology Journal
Brian B Hasinoff
Bortezomib, carfilzomib, ixazomib, oprozomib, and delanzomib are anticancer drugs that target the proteasomal system. Carfilzomib and oprozomib are epoxyketones that form an irreversible covalent bond with the 20S proteasome, whereas bortezomib, ixazomib, and delanzomib are boronic acids that form slowly reversible adducts. The binding kinetics of some of these drugs have either not been well characterized, or have been studied under a variety of different conditions. Utilizing a fluorogenic substrate the kinetics of the slow-binding inhibition of the chymotrypsin-like proteasomal activity of human 20S proteasome was determined under a standard set of conditions in order to compare the kinetic and equilibrium properties of these drugs...
January 2, 2018: Archives of Biochemistry and Biophysics
Anna Piasecka, Honorata Czapinska, Marie-Theres Vielberg, Roman Szczepanowski, Reiner Kiefersauer, Simon Reed, Michael Groll, Matthias Bochtler
Anbu (ancestral β-subunit) is homologous to HslV and 20S proteasomes. Based on its phylogenetic distribution and sequence clustering, Anbu has been proposed as the "ancestral" form of proteasomes. Here, we report biochemical data, small-angle X-ray scattering (SAXS) results, negative stain electron microscopy (EM) micrographs, and a crystal structure of the Anbu particle from Yersinia bercovieri (YbAnbu). All data are consistent with YbAnbu forming defined 12-14 subunit multimers that differ in shape from both HslV and 20S proteasomes...
December 16, 2017: Journal of Molecular Biology
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