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https://www.readbyqxmd.com/read/29790300/aspiration-pneumonia-induces-muscle-atrophy-in-the-respiratory-skeletal-and-swallowing-systems
#1
Riyo Komatsu, Tatsuma Okazaki, Satoru Ebihara, Makoto Kobayashi, Yoko Tsukita, Mayumi Nihei, Hisatoshi Sugiura, Kaijun Niu, Takae Ebihara, Masakazu Ichinose
BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle...
May 22, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29790175/mechanisms-of-cell-regulation-proteolysis-the-big-surprise
#2
Dieter H Wolf, Ruth Menssen
Precise regulation of cellular processes is essential for life. Concerning proteins, many regulatory mechanisms were explored over the years, such as posttranslational modifications (e.g. phosphorylation), enzyme activation or inhibition by small molecules, and modulation of protein-protein interactions. Complete removal of a protein via proteolysis as a regulatory mechanism, however, was denied for a long time, mainly due to economical considerations. Scientists could not believe that a protein which is synthesized at the expense of a lot of energy could be destroyed again...
May 22, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29790151/irreversible-modifications-of-receptor-tyrosine-kinases
#3
Matthew Kreitman, Ashish Noronha, Yosef Yarden
Each group of the 56 receptor tyrosine kinases (RTK) binds with one or more soluble growth factors and coordinates a vast array of cellular functions. These outcomes are tightly regulated by inducible post-translational events, such as tyrosine phosphorylation, ubiquitination, ectodomain shedding and regulated intramembrane proteolysis. Because of the delicate balance required for appropriate RTK function, cells may become pathogenic upon dysregulation of RTKs themselves or their post-translational covalent modifications...
May 22, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29786787/protocols-for-migration-and-invasion-studies-in-prostate-cancer
#4
Arjanneke F van de Merbel, Geertje van der Horst, Jeroen T Buijs, Gabri van der Pluijm
Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29785912/para-%C3%AE%C2%BA-casein-during-the-ripening-and-storage-of-low-ph-high-moisture-feta-cheese
#5
Voula Alexandraki, Golfo Moatsou
The hypothesis of this research paper was that the physicochemical conditions in a low-pH, high-moisture white brined cheese such as Feta would make para-κ-casein vulnerable to residual chymosin activity during ripening and storage. It was important to address this hypothesis, since cheese para-κ-casein could theoretically be used for the assessment of the origin of cheese milk by means of various analytical methods. Feta cheese was manufactured from sheep milk and from four different mixtures of sheep and goat milk in triplicate...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29785402/formyl-met-leu-phe-stimulated-fpr1-phosphorylation-in-plate-adherent-human-neutrophils-enhanced-proteolysis-but-lack-of-inhibition-by-platelet-activating-factor
#6
Algirdas J Jesaitis, Jeannie Gripentrog, Jovanka M Voyich
N-formyl-Met-Leu-Phe (fMLF) is a model PAMP/DAMP driving human PMN to sites of injury/infection utilizing the GPCR, FPR1. We examined a microtiter plate format for measurement of FPR1 phosphorylation in adherent PMN at high densities and found that a new phosphosensitive FPR1 fragment, 25K-FPR1, accumulates in SDS-PAGE extracts. 25K-FPR1 is fully inhibited by diisopropylfluorophosphate PMN pretreatment but is not physiologic, as its formation failed to be significantly perturbed by ATP depletion, time and temperature of adherence, or adherence mechanism...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29784885/-pseudomonas-aeruginosa-regulated-intramembrane-proteolysis-rip-protease-mucp-can-overcome-mutations-in-the-algo-periplasmic-protease-to-restore-alginate-production-in-nonmucoid-revertants
#7
Camila Delgado, Laura Florez, Ivonne Lollett, Christine Lopez, Shiva Kangeyan, Hansi Kumari, Marios Stylianou, Robert J Smiddy, Lisa Schneper, Robert T Sautter, George Szatmari, Kalai Mathee
The progression of cystic fibrosis (CF) from an acute to a chronic disease is often associated with the conversion of the opportunistic pathogen Pseudomonas aeruginosa from a nonmucoid form to a mucoid form in the lung. This conversion involves the overproduction of the exopolysaccharide alginate, whose production is under control of the AlgT/U sigma factor. This factor is regulated posttranslationally by an extremely unstable process and has been commonly attributed to mutations in the algT/U gene. By exploiting this unstable phenotype, we isolated 34 spontaneous nonmucoid variants arising from the mucoid strain PDO300, a PAO1 derivative containing the mucA22 allele commonly found in mucoid CF isolates...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29783208/the-role-of-hydrogen-sulfide-in-the-progression-mechanisms-of-non-alcoholic-steatohepatitis-and-chronic-kidney-disease
#8
Oksana S Khukhlina, Igor V Gerush, Alona A Antoniv, Olha Ye Mandryk, Tamara G Kopchuk, Svitlana P Melnychuk, Zoriana Ia Kotsiubiichuk
OBJECTIVE: Introduction: The steady increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine. The aim: To establish the role of hydrogen sulfide in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 114 patients with NASH were examined on the background of obesity of І-ІІ degree, including: 52 patients with NASH (group 1) (without accompanying CKD), 62 patients with NASH with a comorbid CKD І-ІІ degree (group 2)...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29782494/ubiquitin-dependent-proteolysis-of-cxcl7-leads-to-posterior-longitudinal-ligament-ossification
#9
Michiyo Tsuru, Atsushi Ono, Hideaki Umeyama, Masahiro Takeuchi, Kensei Nagata
Ossification of the posterior longitudinal ligament (OPLL), a spinal ligament, reduces the range of motion in limbs. No treatment is currently available for OPLL, which is why therapies are urgently needed. OPLL occurs in obesity, is more common in men, and has an onset after 40 years of age. The mechanisms underlying OPLL remain unclear. In this study, we performed a serum proteomic analysis in both OPLL patients and healthy subjects to identify factors potentially involved in the development of OPLL, and found reduced levels of a protein that might underlie the pathology of OPLL...
2018: PloS One
https://www.readbyqxmd.com/read/29782000/induction-of-nephrotic-syndrome-in-mice-by-retrobulbar-injection-of-doxorubicin-and-prevention-of-volume-retention-by-sustained-release-aprotinin
#10
Bernhard N Bohnert, Ferruh Artunc
Nephrotic syndrome is the most extreme manifestation of proteinuric kidney disease and characterized by heavy proteinuria, hypoalbuminemia, and edema due to sodium retention and hyperlipidemia. To study the pathophysiology of this syndrome, rodent models have been developed based on the injection of toxic substances such as doxorubicin causing podocyte damage. In mice, only few strains are susceptible to this model. In wildtype 129S1/SvImJ mice, the administration of doxorubicin by rapid intravenous injection to the retrobulbar sinus induces experimental nephrotic syndrome that features all the symptoms of human disease including sodium retention and edema...
May 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29780502/the-impact-of-o-glycan-chemistry-on-the-stability-of-intrinsically-disordered-proteins
#11
Erica T Prates, Xiaoyang Guan, Yaohao Li, Xinfeng Wang, Patrick K Chaffey, Munir S Skaf, Michael F Crowley, Zhongping Tan, Gregg T Beckham
Protein glycosylation is a diverse post-translational modification that serves myriad biological functions. O -linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O -mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions. However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs)...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29779948/the-eukaryotic-proteome-is-shaped-by-e3-ubiquitin-ligases-targeting-c-terminal-degrons
#12
Itay Koren, Richard T Timms, Tomasz Kula, Qikai Xu, Mamie Z Li, Stephen J Elledge
Degrons are minimal elements that mediate the interaction of proteins with degradation machineries to promote proteolysis. Despite their central role in proteostasis, the number of known degrons remains small, and a facile technology to characterize them is lacking. Using a strategy combining global protein stability (GPS) profiling with a synthetic human peptidome, we identify thousands of peptides containing degron activity. Employing CRISPR screening, we establish that the stability of many proteins is regulated through degrons located at their C terminus...
May 11, 2018: Cell
https://www.readbyqxmd.com/read/29777832/novel-cysteine-and-albumin-adduct-biomarkers-to-prove-human-poisoning-with-the-pesticide-oxydemeton-s-methyl
#13
Harald John, Markus Siegert, Florian Eyer, Franz Worek, Horst Thiermann, Andreas Kranawetvogl
We herein report on the forensic analysis of plasma samples to prove human poisoning with oxydemeton-S-methyl (ODM), S-(2-(ethylsulfinyl)ethyl)-O,O-dimethyl phosphorothioate. This organophosphorus pesticide is the active ingredient of Metasystox® , that was swallowed by a 77-year-old woman to commit suicide. ODM belongs to the class of dimethyl phosphoryl (DMP) pesticides, contains a 2-(ethylsulfinyl)ethanethiol (ESOET) leaving group and undergoes adduct formation with endogenous molecules as elaborated herein with human serum exposed to pesticides in vitro...
May 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29777712/speckle-type-poz-protein-suppresses-hepatocellular-carcinoma-cell-migration-and-invasion-via-ubiquitin-dependent-proteolysis-of-sumo1-sentrin-specific-peptidase-7
#14
Piyou Ji, Shaohua Liang, Pengtao Li, Chengrong Xie, Jie Li, Kang Zhang, Xuqing Zheng, Min Feng, Qiu Li, Hui Jiao, Xiaoqin Chi, Wenxiu Zhao, Sheng Zhang, Xiaomin Wang
Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777136/functional-proteomic-profiling-of-secreted-serine-proteases-in-health-and-inflammatory-bowel-disease
#15
Alexandre Denadai-Souza, Chrystelle Bonnart, Núria Solà Tapias, Marlène Marcellin, Brendan Gilmore, Laurent Alric, Delphine Bonnet, Odile Burlet-Schiltz, Morley D Hollenberg, Nathalie Vergnolle, Céline Deraison
While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777089/human-plasma-and-serum-extracellular-small-rna-reference-profiles-and-their-clinical-utility
#16
Klaas E A Max, Karl Bertram, Kemal Marc Akat, Kimberly A Bogardus, Jenny Li, Pavel Morozov, Iddo Z Ben-Dov, Xin Li, Zachary R Weiss, Azadeh Azizian, Anuoluwapo Sopeyin, Thomas G Diacovo, Catherine Adamidi, Zev Williams, Thomas Tuschl
Circulating extracellular RNAs (exRNAs) have the potential to serve as biomarkers for a wide range of medical conditions. However, limitations in existing exRNA isolation methods and a lack of knowledge on parameters affecting exRNA variability in human samples may hinder their successful discovery and clinical implementation. Using combinations of denaturants, reducing agents, proteolysis, and revised organic extraction, we developed an automated, high-throughput approach for recovery of exRNAs and exDNA from the same biofluid sample...
May 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29775708/gelatin-alginate-coacervates-for-circumventing-proteolysis-and-probing-intermolecular-interactions-by-spr
#17
Hui-Chong Lau, Seonghee Jeong, Aeri Kim
Complex coacervates based on natural biopolymers have been explored as a protein delivery system to provide controlled release of loaded protein and circumvent its proteolytic degradation in chronic wounds. The coacervates composed of gelatin A (GA) and sodium alginate (SA) were optimized with respect to turbidity, size, zeta potential, and polydispersity index. Bovine serum albumin (BSA), a model protein, was effectively encapsulated in the coacervates, resulting in protection from trypsin digestion and controlled release...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775578/c-terminal-end-directed-protein-elimination-by-crl2-ubiquitin-ligases
#18
Hsiu-Chuan Lin, Chi-Wei Yeh, Yen-Fu Chen, Ting-Ting Lee, Pei-Yun Hsieh, Domnita V Rusnac, Sung-Ya Lin, Stephen J Elledge, Ning Zheng, Hsueh-Chi S Yen
The proteolysis-assisted protein quality control system guards the proteome from potentially detrimental aberrant proteins. How miscellaneous defective proteins are specifically eliminated and which molecular characteristics direct them for removal are fundamental questions. We reveal a mechanism, DesCEND (destruction via C-end degrons), by which CRL2 ubiquitin ligase uses interchangeable substrate receptors to recognize the unusual C termini of abnormal proteins (i.e., C-end degrons). C-end degrons are mostly less than ten residues in length and comprise a few indispensable residues along with some rather degenerate ones...
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29774745/interplay-between-copper-neprilysin-and-n-truncation-of-%C3%AE-amyloid
#19
Mariusz Mital, Wojciech Bal, Tomasz Frączyk, Simon C Drew
Sporadic Alzheimer's disease (AD) is associated with an inefficient clearance of the β-amyloid (Aβ) peptide from the central nervous system. The protein levels and activity of the Zn2+ -dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD. The present study considered the ability of Cu2+ ions to inhibit human recombinant NEP and the role for NEP in generating N-truncated Aβ fragments with high-affinity Cu2+ binding motifs that can prevent this inhibition...
May 18, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29774130/targeting-invadopodia-mediated-breast-cancer-metastasis-by-using-abl-kinase-inhibitors
#20
Tomer Meirson, Alessandro Genna, Nikola Lukic, Tetiana Makhnii, Joel Alter, Ved P Sharma, Yarong Wang, Abraham O Samson, John S Condeelis, Hava Gil-Henn
Metastatic dissemination of cancer cells from the primary tumor and their spread to distant sites in the body is the leading cause of mortality in breast cancer patients. While researchers have identified treatments that shrink or slow metastatic tumors, no treatment that permanently eradicates metastasis exists at present. Here, we show that the ABL kinase inhibitors imatinib, nilotinib, and GNF-5 impede invadopodium precursor formation and cortactin-phosphorylation dependent invadopodium maturation, leading to decreased actin polymerization in invadopodia, reduced extracellular matrix degradation, and impaired matrix proteolysis-dependent invasion...
April 24, 2018: Oncotarget
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