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https://www.readbyqxmd.com/read/28723894/cysteine-protease-cathepsin-b-mediates-radiation-induced-bystander-effects
#1
Yu Peng, Man Zhang, Lingjun Zheng, Qian Liang, Hanzeng Li, Jeng-Ting Chen, Hongyan Guo, Sawako Yoshina, Yu-Zen Chen, Xiang Zhao, Xiaoqi Wu, Bin Liu, Shohei Mitani, Jau-Song Yu, Ding Xue
The radiation-induced bystander effect (RIBE) refers to a unique process in which factors released by irradiated cells or tissues exert effects on other parts of the animal not exposed to radiation, causing genomic instability, stress responses and altered apoptosis or cell proliferation. Although RIBEs have important implications for radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain poorly understood. Here we use Caenorhabditis elegans as a model in which to study RIBEs, and identify the cysteine protease CPR-4, a homologue of human cathepsin B, as the first RIBE factor in nematodes, to our knowledge...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28720501/numb-positively-regulates-autophagic-flux-via-regulating-lysosomal-function
#2
Haiyan Sun, Yi Liu, Lei Zhang, Ximing Shao, Ke Liu, Zhihao Ding, Xianming Liu, Huashun Li, Hongchang Li
Autophagy is a lysosome-dependent catabolic process involving in the degradation and recycling of unnecessary or damaged proteins and organelles. Emerging evidence indicates that autophagy dysfunction is closely related to various human diseases including cancer, aging, myopathies and neurodegenerative disorders. Here, using genetic knockdown, we uncover the role of Numb, an endocytic adaptor protein, in regulating the late steps of autophagy. We found that Numb depletion led to the accumulation of autophagic vacuole, as verified by RFP-LC3 staining combined with transmission electron microscopy...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28720327/asymmetric-synthesis-and-evaluation-of-epoxy-%C3%AE-acyloxycarboxamides-as-selective-inhibitors-of-cathepsin-l
#3
Deborah A Dos Santos, Anna Maria Deobald, Vivian E Cornelio, Roberta M D Ávila, Renata C Cornea, Gilberto C R Bernasconi, Marcio W Paixão, Paulo C Vieira, Arlene G Corrêa
Cathepsin L plays important roles in physiological processes as well as in the development of many pathologies. Recently the attentions were turned to its association with tumor progress what makes essential the development of more potent and selective inhibitors. In this work, epoxipeptidomimetics were investigated as new cathepsin inhibitors. This class of compounds is straightforward obtained by using a green one-pot asymmetric epoxidation/Passerini 3-MCR. A small library of 17 compounds was evaluated against cathepsin L, and among them LSPN423 showed to be the most potent...
June 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28713775/salivary-tick-cystatin-omc2-targets-lysosomal-cathepsins-s-and-c-in-human-dendritic-cells
#4
Tina Zavašnik-Bergant, Robert Vidmar, Andreja Sekirnik, Marko Fonović, Jiří Salát, Lenka Grunclová, Petr Kopáček, Boris Turk
To ensure successful feeding tick saliva contains a number of inhibitory proteins that interfere with the host immune response and help to create a permissive environment for pathogen transmission. Among the potential targets of the salivary cystatins are two host cysteine proteases, cathepsin S, which is essential for antigen- and invariant chain-processing, and cathepsin C (dipeptidyl peptidase 1, DPP1), which plays a critical role in processing and activation of the granule serine proteases. Here, the effect of salivary cystatin OmC2 from Ornithodoros moubata was studied using differentiated MUTZ-3 cells as a model of immature dendritic cells of the host skin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28713240/the-coordinated-action-of-calcineurin-and-cathepsin-d-protects-against-%C3%AE-synuclein-toxicity
#5
Andreas Aufschnaiter, Lukas Habernig, Verena Kohler, Jutta Diessl, Didac Carmona-Gutierrez, Tobias Eisenberg, Walter Keller, Sabrina Büttner
The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca(2+) homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28707576/new-strategies-for-the-prevention-and-treatment-of-systemic-and-local-bone-loss-from-pathophysiology-to-clinical-application
#6
A Fassio, Maurizio Rossini, Ombretta Viapiana, Luca Idolazzi, Camilla Benini, Elisabetta Vantaggiato, Davide Gatti
Bone loss is the result of a negative unbalance between bone formation ad bone resorption. In the last years, the studies on the Wnt canonical pathway have highlighted its crucial role in bone balance through its influence on the activity and maturation of the osteoblast line and in the Receptor Activator of Nuclear Factor κ B (RANK) - RANK ligand (RANKL)/Osteoprotegerin (OPG) system. These mechanisms are involved not only in the pathological processes inducing not only systemic bone loss (ie. Postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, etc...
July 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28705721/characterization-of-nlrp3-like-gene-from-apostichopus-japonicus-provides-new-evidence-on-inflammation-response-in-invertebrates
#7
Zhimeng Lv, Zhixin Wei, Zhen Zhang, Chenghua Li, Yina Shao, Weiwei Zhang, Xuelin Zhao, Ye Li, Xuemei Duan, Jinbo Xiong
Inflammatory/defensive response after pathogen invasion is considered a local defense reaction in vertebrates. Inflammation response in Apostichopus japonicus was hardly determined due to scarce information available for nucleotide binding domain-like receptor family, pyrin domain-containing (NLRP) family. In the present study, invertebrate NLRP homologue was identified from A. japonicus (designated as AjNLRP3-like) by rapid amplification of cDNA ends. Full-length cDNA of AjNLRP3-like measured 2970 bp with 2265 bp open reading frame encoding a 754-amino acid (aa) residue protein...
July 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28703794/impaired-autophagosome-clearance-contributes-to-neuronal-death-in-a-piglet-model-of-neonatal-hypoxic-ischemic-encephalopathy
#8
Derong Cui, Dawei Sun, Xintao Wang, Liye Yi, Ewa Kulikowicz, Michael Reyes, Junchao Zhu, Zeng-Jin Yang, Wei Jiang, Raymond C Koehler
To examine the temporal relationship of cortical autophagic flux with delayed neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets. Markers of autophagic, lysosomal and cell death signaling were studied via immunohistochemistry, immunoblotting, and histochemistry in piglet brains. In vitro, autophagy was impaired in cultured mouse cortical neurons treated with chloroquine with or without rapamycin for 1 d in the presence of Z-VAD-fmk, cyclosporine A, or vehicle control, and cell viability was assessed with the MTT assay...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28702507/brainstem-phenotype-of-cathepsin-a-related-arteriopathy-with-strokes-and-leukoencephalopathy
#9
Yun Tae Hwang, Rahul Lakshmanan, Indran Davagnanam, Andrew G B Thompson, David S Lynch, Henry Houlden, Nin Bajaj, Sofia H Eriksson, Doris-Eva Bamiou, Jason D Warren
No abstract text is available yet for this article.
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28699744/design-synthesis-and-pharmacokinetics-of-a-bone-targeting-dual-action-prodrug-for-treatment-of-osteoporosis
#10
Haibo Xie, Gang Chen, Robert N Young
A dual-action bone-targeting prodrug has been designed, synthesized and evaluated for in vitro and in vivo metabolic stability and in vivo tissue distribution, and rates of release of the active constituents after binding to bones through the use of differentially double labelled derivatives. The conjugate (general structure 7) embodies the merger of a very potent and proven anabolic selective agonist of the prostaglandin EP4 receptor, compound 5, and alendronic acid, a potent inhibitor of bone resorption, optimally linked through a differentially hydrolyzable linker unit, N-4-carboxymethylphenyl-methyloxycarbonyl-leucinyl-argininyl-para-aminophenylmethylalcohol (Leu-Arg-PABA)...
July 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28699722/antinociceptive-anti-inflammatory-and-antiarthritic-activities-of-bungarus-fasciatus-venom-in-experimental-animal-models
#11
Susmita Ghosh, Partha Pratim Saha, Subir C Dasgupta, Antony Gomes
Pain and inflammation are intimately associated with rheumatoid arthritis, a growing bone-joint related problem of the modern society. Though several therapeutic managements are available for arthritis, their side effects not only limit their use, but also advocate the quest for natural therapies. In this study, we explored the antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom (BFV) in experimental animal models. Rheumatoid arthritis was induced by Freund’s complete adjuvant (FCA) in male Wistar albino rats...
September 2016: Indian Journal of Experimental Biology
https://www.readbyqxmd.com/read/28698143/snail-transcription-factor-nls-and-importin-%C3%AE-1-regulate-the-subcellular-localization-of-cathepsin-l-and-cux1
#12
Liza J Burton, Veronica Henderson, Latiffa Liburd, Valerie A Odero-Marah
Several recent studies have highlighted an additional unexpected localization and site of action for Cathepsin L (Cat L) protease within the nucleus in breast, colon and prostate cancer, however, its role in the nucleus was unclear. It was proposed to mediate proteolytic processing of the transcription factor CCAAT-displacement protein/cut homeobox transcription factor (Cux1) from the full-length p200 isoform to generate the p110 and p90 isoforms, of which the p110 isoform was shown to act as a cell cycle regulator to accelerate entry into the S phase...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28698054/bistacrines-as-potential-antitrypanosomal-agents
#13
Ines Schmidt, Sarah Göllner, Antje Fuß, August Stich, Anna Kucharski, Tanja Schirmeister, Elena Katzowitsch, Heike Bruhn, Alexandra Miliu, R Luise Krauth-Siegel, Ulrike Holzgrabe
Human African Trypanosomiasis (HAT) is caused by two subspecies of the genus Trypanosoma, namely Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. The disease is fatal if left untreated and therapy is limited due to only five non-adequate drugs currently available. In preliminary studies, dimeric tacrine derivatives were found to inhibit parasite growth with IC50-values in the nanomolar concentration range. This prompted the synthesis of a small, but smart library of monomeric and dimeric tacrine-type compounds and their evaluation of antiprotozoal activity...
July 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28697819/functional-characterization-of-single-domain-cystatin-like-cysteine-proteinase-inhibitors-expressed-by-the-trematode-fasciola-hepatica
#14
Martín Cancela, Ileana Corvo, Edileuza DA Silva, Aline Teichmann, Leda Roche, Alvaro Díaz, José Fransisco Tort, Henrique B Ferreira, Arnaldo Zaha
Cystatins are small, phylogenetically conserved proteins that are tight-binding inhibitors of cysteine proteinases. The liver fluke Fasciola hepatica uses a diverse set of cysteine proteinases of the papain superfamily for host invasion, immune evasion and nutrition, but little is known about the regulation of these enzymes. The aim of this work is to characterize the cystatin repertoire of F. hepatica. For this purpose, we first surveyed the available sequence databases, identifying three different F. hepatica single-domain cystatins...
July 12, 2017: Parasitology
https://www.readbyqxmd.com/read/28697272/screening-of-antigenic-vesicular-fluid-proteins-of-echinococcus-multilocularis-as-potential-viability-biomarkers-to-monitor-drug-response-in-alveolar-echinococcosis-patients
#15
Benoît Valot, Bénédicte Rognon, Anais Prenel, Alice Baraquin, Jenny Knapp, Mathilde Anelli, Carine Richou, Solange Bresson-Hadni, Frederic Grenouillet, Junhua Wang, Dominique Angèle Vuitton, Bruno Gottstein, Laurence Millon
PURPOSE: The only drugs available to treat alveolar echinococcosis (AE) are mostly parasitostatic and in many cases prescribed for life. Decision criteria for discontinuation rely on the absence of parasitic viability. The aim of the present study was to search for candidate proteins that may exhibit good potential as biomarkers for viability. EXPERIMENTAL DESIGN: Sixteen serum samples (5 healthy controls,11 patients with AE), were used. AE-patients were classified into 3 groups 'Cured' (n = 2), 'ABZ-responders' (n = 4) and 'ABZ-non responders' (n = 5)...
July 11, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28697174/uv-radiation-promotes-melanoma-dissemination-mediated-by-the-sequential-reaction-axis-of-cathepsins-tgf-%C3%AE-1-fap-%C3%AE
#16
Petra Wäster, Kyriakos Orfanidis, Ida Eriksson, Inger Rosdahl, Oliver Seifert, Karin Öllinger
BACKGROUND: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed. METHODS: Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs...
July 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28696515/tbhq-suppresses-osteoclastic-resorption-in-xenogeneic-treated-dentin-matrix-based-scaffolds
#17
Jingjing Sun, Jie Li, Hui Li, Hefeng Yang, Jinlong Chen, Bo Yang, Fangjun Huo, Weihua Guo, Weidong Tian
Extracellularmatrix (ECM)-based scaffolds are important for their potential therapeutic application. Treated dentin matrix (TDM), a kind of ECM, seeded with allogeneic dental follicle stem cells (TDM/aDFC) provides a suitable inductive microenvironment for tooth root regeneration. Considering the limited sources, xenogeneic TDM (xTDM) is a possible alternative to allogeneic TDM; however, xTDM-based scaffold presents severe osteolysis and resorption lacunae causing regenerated tooth root failure. Immune response-induced excessive osteoclastogenesis plays a critical role in xenogeneic scaffold osteolysis and resorption...
July 11, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28694354/myocardial-upregulation-of-cathepsin-d-by-ischemic-heart-disease-promotes-autophagic-flux-and-protects-against-cardiac-remodeling-and-heart-failure
#18
Penglong Wu, Xun Yuan, Faqian Li, Jianhua Zhang, Wei Zhu, Meng Wei, Jingbo Li, Xuejun Wang
BACKGROUND: Lysosomal dysfunction is implicated in human heart failure for which ischemic heart disease is the leading cause. Altered myocardial expression of CTSD (cathepsin D), a major lysosomal protease, was observed in human heart failure, but its pathophysiological significance has not been determined. METHODS AND RESULTS: Western blot analyses revealed an increase in the precursor but not the mature form of CTSD in myocardial samples from explanted human failing hearts with ischemic heart disease, which is recapitulated in chronic myocardial infarction produced via coronary artery ligation in Ctsd(+/+) but not Ctsd(+/-) mice...
July 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28694149/host-regulation-by-the-ectophagous-parasitoid-wasp-bracon-nigricans
#19
Andrea Becchimanzi, Maddalena Avolio, Ilaria Di Lelio, Adriana Marinelli, Paola Varricchio, Annalisa Grimaldi, Magda de Eguileor, Francesco Pennacchio, Silvia Caccia
The host regulation process has been widely investigated in endophagous parasitoid wasps, which in most cases finely interact with living hosts (i.e. koinobiont parasitoids). In contrast, only very limited information is available for ectophagous parasitoids that permanently paralyze and rapidly suppress their victims (i.e. idiobiont parasitoids). Here we try to fill this research gap by investigating the host regulation by Bracon nigricans, an ectophagous idiobiont wasp species. Parasitism, mainly by venom action, is able to redirect host metabolism in order to enhance its nutritional suitability for the developing parasitoid larvae and to provide the required metabolic support to host tissues...
July 8, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28693471/spatial-pattern-analysis-of-nuclear-migration-in-remodelled-muscles-during-drosophila-metamorphosis
#20
Kuleesha, Lin Feng, Martin Wasser
BACKGROUND: Many human muscle wasting diseases are associated with abnormal nuclear localization. During metamorphosis in Drosophila melanogaster, multi-nucleated larval dorsal abdominal muscles either undergo cell death or are remodeled to temporary adult muscles. Muscle remodeling is associated with anti-polar nuclear migration and atrophy during early pupation followed by polar migration and muscle growth during late pupation. Muscle remodeling is a useful model to study genes involved in myonuclear migration...
July 10, 2017: BMC Bioinformatics
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