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cathepsin d

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https://www.readbyqxmd.com/read/28646121/at1-receptor-blockade-attenuates-outward-aortic-remodeling-associated-with-diet-induced-obesity-in-mice
#1
Friedrich Krueger, Kai Kappert, Anna Foryst-Ludwig, Frederike Kramer, Markus Clemenz, Aleksandra Grzesiak, Manuela Sommerfeld, Jan Paul Bernhard Frese, Andreas Greiner, Ulrich Kintscher, Thomas Unger, Elena Kaschina
The renin-angiotensin-system and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are yet not understood. We investigated the effect of the angiotensin AT1-receptor antagonist telmisartan on aortic outward remodeling in a diet-induced obesity-model in mice. C57/Black6J mice were fed with either a low-fat diet (LFD), or a high-fat diet (HFD) for 14 weeks. One group of HFD-mice was additionally exposed to telmisartan (3mg/kg/d) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibres, and decreased elastin content...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28644993/long-term-toxicity-of-surface-charged-polystyrene-nanoplastics-to-marine-planktonic-species-dunaliella-tertiolecta-and-artemia-franciscana
#2
E Bergami, S Pugnalini, M L Vannuccini, L Manfra, C Faleri, F Savorelli, K A Dawson, I Corsi
Plastic pollution has been globally recognized as a critical issue for marine ecosystems and nanoplastics constitute one of the last unexplored areas to understand the magnitude of this threat. However, current difficulties in sampling and identifying nano-sized debris make hard to assess their occurrence in marine environment. Polystyrene nanoparticles (PS NPs) are largely used as nanoplastics in ecotoxicological studies and although acute exposures have been already investigated, long-term toxicity on marine organisms is unknown...
June 15, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28634469/alexander-disease-mutations-produce-cells-with-coexpression-of-glial-fibrillary-acidic-protein-and-ng2-in-neurosphere-cultures-and-inhibit-differentiation-into-mature-oligodendrocytes
#3
Ulises Gómez-Pinedo, Maria Salomé Sirerol-Piquer, María Durán-Moreno, José Manuel García-Verdugo, Jorge Matias-Guiu
BACKGROUND: Alexander disease (AxD) is a rare disease caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). The disease is characterized by presence of GFAP aggregates in the cytoplasm of astrocytes and loss of myelin. OBJECTIVES: Determine the effect of AxD-related mutations on adult neurogenesis. METHODS: We transfected different types of mutant GFAP into neurospheres using the nucleofection technique. RESULTS: We find that mutations may cause coexpression of GFAP and NG2 in neurosphere cultures, which would inhibit the differentiation of precursors into oligodendrocytes and thus explain the myelin loss occurring in the disease...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28625714/proteomic-analysis-of-seminal-plasma-from-locally-adapted-curraleiro-p%C3%A3-duro-bulls-bos-taurus-identifying-biomarkers-involved-in-sperm-physiology-in-endangered-animals-for-conservation-of-biodiversity
#4
E B Menezes, R V de Oliveira, M F van Tilburg, E A Barbosa, N V Nascimento, A L M C S Velho, F B Moreno, R A Moreira, A C O Monteiro-Moreira, G M C Carvalho, A F Ramos, E Memili, A A Moura
The present study was aimed at evaluating the seminal plasma proteins and sperm parameters of Curraleiro Pé-Duro bulls. Semen was collected from 10 bulls by electroejaculation, and sperm parameters were evaluated in fresh and frozen-thawed semen. Seminal plasma proteins were analyzed by 2-D SDS-PAGE and mass spectrophotometry. Tools in computational biology were used to generate bioinformatic knowledge and evaluate gene ontology, protein-protein interactions, phylogenetic trees and multiple sequence alignments...
May 29, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28618037/hydrogen-peroxide-stimulates-exosomal-cathepsin-b-regulation-of-the-receptor-for-advanced-glycation-end-products-rage
#5
Charles A Downs, Viet D Dang, Nicholle M Johnson, Nancy Denslow, Abdel A Alli
Exosomes are nano-sized vesicles that are secreted into the extracellular environment. These vesicles contain various biological effector molecules that can regulate intracellular signaling pathways in recipient cells. The aim of this study was to examine a correlation between exosomal cathepsin B activity and the receptor for advanced glycation end-products (RAGE). Type 1 alveolar epithelial (R3/1) cells were treated with or without hydrogen peroxide and exosomes isolated from the cell conditioned media were characterized by NanoSight analysis...
June 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28615690/cathepsin-d-regulates-lipid-metabolism-in-murine-steatohepatitis
#6
Tom Houben, Yvonne Oligschlaeger, Tim Hendrikx, Albert V Bitorina, Sofie M A Walenbergh, Patrick J van Gorp, Marion J J Gijbels, Silvia Friedrichs, Jogchum Plat, Frank G Schaap, Dieter Lütjohann, Marten H Hofker, Ronit Shiri-Sverdlov
Due to the obesity epidemic, non-alcoholic steatohepatitis (NASH) is a prevalent liver disease, characterized by fat accumulation and inflammation of the liver. However, due to a lack of mechanistic insight, diagnostic and therapeutic options for NASH are poor. Recent evidence has indicated cathepsin D (CTSD), a lysosomal enzyme, as a marker for NASH. Here, we investigated the function of CTSD in NASH by using an in vivo and in vitro model. In addition to diminished hepatic inflammation, inhibition of CTSD activity dramatically improved lipid metabolism, as demonstrated by decreased plasma and liver levels of both cholesterol and triglycerides...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611989/expression-of-cathepsins-b-d-and-g-in-isocitrate-dehydrogenase-wildtype-glioblastoma
#7
Sabrina P Koh, Agadha C Wickremesekera, Helen D Brasch, Reginald Marsh, Swee T Tan, Tinte Itinteang
AIM: To investigate the expression of cathepsins B, D, and G, in relation to the cancer stem cell (CSC) subpopulations, we have previously characterized within isocitrate dehydogenase (IDH)-wildtype glioblastoma (IDHWGB). METHODS: 3,3-Diaminobezidine (DAB) immunohistochemical (IHC) staining for cathepsins B, D, and G, was performed on 4μm-thick formalin-fixed paraffin-embedded IDHWGB samples obtained from six patients. Two representative DHWGB samples from the original cohort of patients were selected for immunofluorescent (IF) IHC staining, to identify the localization of the cathepsins in relation to the CSC subpopulations...
2017: Frontiers in Surgery
https://www.readbyqxmd.com/read/28594408/autophagy-blockade-and-lysosomal-membrane-permeabilization-contribute-to-lead-induced-nephrotoxicity-in-primary-rat-proximal-tubular-cells
#8
Xiang-Bin Song, Gang Liu, Fei Liu, Zhen-Gui Yan, Zhen-Yong Wang, Zong-Ping Liu, Lin Wang
Lead (Pb) is a known nephrotoxicant that causes damage to proximal tubular cells. Autophagy has an important protective role in various renal injuries, but the role of autophagy in Pb-elicited nephrotoxicity remains largely unknown. In this study, Pb promoted the accumulation of autophagosomes in primary rat proximal tubular (rPT) cells, and subsequent findings revealed that this autophagosome accumulation was caused by the inhibition of autophagic flux. Moreover, Pb exposure did not affect the autophagosome-lysosome fusion in rPT cells...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28588449/long-term-assessment-of-aav-mediated-zinc-finger-nuclease-expression-in-the-mouse-brain
#9
Muzna Zahur, Johan Tolö, Mathias Bähr, Sebastian Kügler
Gene editing tools like TALENs, ZFNs and Crispr/Cas now offer unprecedented opportunities for targeted genetic manipulations in virtually all species. Most of the recent research in this area has concentrated on manipulation of the genome in isolated cells, which then give rise to transgenic animals or modified stem cell lines. Much less is known about applicability of genetic scissors in terminally differentiated, non-dividing cells like neurons of the adult brain. We addressed this question by expression of a pair of ZFNs targeting the murine cathepsin D gene in CNS neurons by means of an optimized AAV viral vector...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28585417/cyanobacterial-peptides-as-a-prototype-for-the-design-of-cathepsin-d-inhibitors
#10
Hao Xu, Keting Bao, Shuai Tang, Jing Ai, Haiyan Hu, Wei Zhang
Cathepsin D (Cath D) is overexpressed and secreted in a number of solid tumors and involved in the progress of tumor invasion, proliferation, metastasis, and apoptosis. Inhibition of Cath D is regarded as an attractive pathway for the development of novel anticancer drugs. Our previous studies revealed that tasiamide B, a cyanobacterial peptide that contained a statine-like unit, exhibited good inhibition against Cath D and other aspartic proteases. Using this natural product as prototype, we designed and synthesized three new analogs, which bear isophthalic acid fragment at the N-terminus and isobutyl amine (1), cyclopropyl amine (2), or 3-methoxybenzyl amine (3) moiety at the C-terminus...
June 6, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28580393/estrogen-depletion-and-drug-treatment-alter-the-microstructure-of-type-i-collagen-in-bone
#11
Meagan A Cauble, Matthew J Muckley, Ming Fang, Jeffrey A Fessler, Kathleen Welch, Edward D Rothman, Bradford G Orr, Le T Duong, Mark M Banaszak Holl
The impact of estrogen depletion and drug treatment on type I collagen fibril nanomorphology and collagen fibril packing (microstructure) was evaluated by atomic force microscopy (AFM) using an ovariectomized (OVX) rabbit model of estrogen deficiency induced bone loss. Nine month-old New Zealand white female rabbits were treated as follows: sham-operated (Sham; n = 11), OVX + vehicle (OVX + Veh; n = 12), OVX + alendronate (ALN, 600 μg/kg/wk., s.c.; n = 12), and OVX + cathepsin-K inhibitor L-235 (CatKI, 10 mg/kg, daily, p...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28579388/targeting-cysteine-proteases-in-trypanosomatid-disease-drug-discovery
#12
REVIEW
Leonardo G Ferreira, Adriano D Andricopulo
Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including infectivity to the human host...
June 1, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28577094/local-and-systemic-functional-responses-of-mouse-macrophages-to-intravaginal-infection-with-type-2-herpes-simplex-virus-and-vaccination
#13
L G Zaitseva, V A Bekhalo, I V Kireeva, G M Shaposhnikova, E V Nagurskaya, I F Barinskii, V G Nesterenko
Activity of cathepsin D and phagocytosis of macrophages from vaginal lavage fluid, peritoneal exudation, and spleen were studied in mice of sensitive (DBA/2) and resistant (BALB/c) lines after intravaginal infection with type 2 herpes simplex virus and vaccination. Activity of cathepsin D and intensity of phagocytosis (irrespective of the macrophage source) and their ratio in BALB/c mice in early terms after infection were close to the control levels taken as a unit. In DBA/2 mice, these parameters and their balance were shifted and changes in cathepsin D activity depended on the time after challenge...
June 3, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28575856/trans-4-4-dihydroxystilbene-dhs-inhibits-human-neuroblastoma-tumor-growth-and-induces-mitochondrial-and-lysosomal-damages-in-neuroblastoma-cell-lines
#14
Bhaskar Saha, Birija Sankar Patro, Mrunesh Koli, Ganesh Pai, Jharna Ray, Sandip K Bandyopadhyay, Subrata Chattopadhyay
In view of the inadequacy of neuroblastoma treatment, five hydroxystilbenes and resveratrol (Resv) were screened for their cytotoxic property against human neuroblastoma cell lines. The mechanism of cytotoxic action of the most potent compound, trans-4,4'-dihydroxystilbene (DHS) was investigated in vitro using human neuroblastoma cell lines. DHS was also tested in a mouse xenograft model of human neuroblastoma tumor. The MTT, sub-G1, annexin V and clonogenic assays as well as microscopy established higher cytotoxicity of DHS than Resv to the IMR32 cell line...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28555835/antiproliferative-and-antimicrobial-efficacy-of-the-compounds-isolated-from-the-roots-of-oenothera-biennis-l
#15
Shilpi Singh, Vijaya Dubey, Dhananjay Kumar Singh, Kaneez Fatima, Ateeque Ahmad, Suaib Luqman
BACKGROUND: Oenothera biennis L., commonly known as evening primrose, harbours the flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of biological activity, such as antitumour, anti-arthritic and anti-inflammatory effects. In addition to the previous reports from aerial parts of this plant, studies related to antiproliferative or antimicrobial activity from the roots are warranted. OBJECTIVE: To investigate antiproliferative and antimicrobial activity of compounds/mixture (1-8) isolated and characterized from the roots of O...
May 29, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28549901/degradation-of-proteoglycan-4-lubricin-by-cathepsin-s-potential-mechanism-for-diminished-ocular-surface-lubrication-in-sj%C3%A3-gren-s-syndrome
#16
Suresh C Regmi, Michael L Samsom, Miriam L Heynen, Gregory D Jay, Benjamin D Sullivan, Sruthi Srinivasan, Barbara Caffery, Lyndon Jones, Tannin A Schmidt
Sjögren's syndrome (SS) is an autoimmune disease affecting the lacrimal and salivary glands with hallmark clinical symptoms of dry eye and dry mouth. Recently, markedly increased cathepsin S (CTSS) activity has been observed in the tears of SS patients. Proteoglycan 4 (PRG4), also known as lubricin, is an effective boundary lubricant that is naturally present on the ocular surface. While PRG4 is susceptible to proteolytic digestion, the potential effect of CTSS on PRG4 remains unknown. The objective of this study was to assess the ability of CTSS to enzymatically degrade purified PRG4, and PRG4 naturally present in human tears, and alter ocular surface boundary lubricating properties...
May 23, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28547657/compartmentalized-expression-patterns-of-pancreatic-and-gastric-related-genes-in-the-alimentary-canal-of-the-ascidian-ciona-intestinalis-evolutionary-insights-into-the-functional-regionality-of-the-gastrointestinal-tract-in-olfactores
#17
Satoshi Nakayama, Michio Ogasawara
Many heterotrophic animals have a one-way alimentary canal that is essential for their nutrition and sequential steps of the digestive system, namely ingestion, digestion, absorption and elimination, are widely shared among bilaterians. Morphological, functional and molecular knowledge of the alimentary canal has been obtained in particular from mammalian research but the shared features and evolution of these aspects of the highly diverged alimentary canal in the animal kingdom are still unclear. We therefore investigate spatial gene expression patterns of pancreatic- and gastric-related molecules of ascidians (a sister group of vertebrates) with special reference to the functional regionality of the gastrointestinal tract...
May 25, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28543404/tumor-necrosis-factor-%C3%AE-induced-apoptosis-in-u937-cells-promotes-cathepsin-d-independent-stefin-b-degradation
#18
Katja Bidovec, Janja Božič, Iztok Dolenc, Boris Turk, Vito Turk, Veronika Stoka
Lysosomal cathepsins were previously found to be involved in tumor necrosis factor-α (TNFα)-induced apoptosis. However, there are opposing views regarding their role as either initiators or amplifiers of the signaling cascade as well as the order of molecular events during this process. In this study, we investigated the role of cathepsin D (catD) in TNFα/cycloheximide-induced apoptosis in U937 human monocytic cells. TNFα-induced apoptosis proceeds through caspase-8 activation, processing of the pro-apoptotic molecule Bid, mitochondrial membrane permeabilization, and caspase-3 activation...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542623/gallium-nanoparticles-facilitate-phagosome-maturation-and-inhibit-growth-of-virulent-mycobacterium-tuberculosis-in-macrophages
#19
Seoung-Ryoung Choi, Bradley E Britigan, David M Moran, Prabagaran Narayanasamy
New treatments and novel drugs are required to counter the growing problem of drug-resistant strains of Mycobacterium tuberculosis (M.tb). Our approach against drug resistant M.tb, as well as other intracellular pathogens, is by targeted drug delivery using nanoformulations of drugs already in use, as well as drugs in development. Among the latter are gallium (III) (Ga)-based compounds. In the current work, six different types of Ga and rifampin nanoparticles were prepared in such a way as to enhance targeting of M...
2017: PloS One
https://www.readbyqxmd.com/read/28526399/evaluation-of-the-effectiveness-of-chronic-antidepressant-drug-treatments-in-the-hippocampal-mitochondria-a-proteomic-study-in-an-animal-model-of-depression
#20
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Rafał Olszanecki, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
Several lines of evidence indicate that adverse experience in early life may be a triggering factor for disturbances in the brain mitochondrial proteins and lead to the development of depression in adulthood. On the other hand, little is known about the impact of chronic administration of various antidepressant drugs on the brain mitochondria, as a target for the pharmacotherapy of depression. The purpose of our study was to compare the impact of chronic treatment with two antidepressant drugs with different mechanisms of action, a tricyclic antidepressant (TCA), imipramine, and an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, fluoxetine, on the mitochondria-enriched subproteome profile in the hippocampus of 3-month-old male rats following a prenatal stress procedure (an animal model of depression)...
May 17, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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