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cathepsin d

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https://www.readbyqxmd.com/read/28733353/use-of-proteomics-to-investigate-kidney-function-decline-over-5-years
#1
Axel C Carlsson, Erik Ingelsson, Johan Sundström, Juan Jesus Carrero, Stefan Gustafsson, Tobias Feldreich, Markus Stenemo, Anders Larsson, Lars Lind, Johan Ärnlöv
BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR...
July 21, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28726323/characterization-of-a-cathepsin-d-protease-from-cho-cell-free-medium-and-mitigation-of-its-impact-on-the-stability-of-a-recombinant-therapeutic-protein
#2
Amareth Lim, Brandon L Doyle, Gerard M Kelly, Angelia M Reed-Bogan, Lawrence H Breen, Parviz A Shamlou, Peter K Lambooy
During purification process development of a recombinant therapeutic protein, an endoproteolytic activity endogenous to the Chinese hamster ovary (CHO) cells and leading to degradation at particular hydrophobic amino acid residues (e.g., Phe and Trp) was observed when processing at acidic pH. The presence of residual levels of protease activity in purified protein batches affected the inherent activity of the product when stored as a solution. In order to develop a robust purification strategy to minimize this undesirable impact, identification and characterization of this protease was essential to ultimately ensure that a solution formulation was stable for many years...
July 20, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28720501/numb-positively-regulates-autophagic-flux-via-regulating-lysosomal-function
#3
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
#4
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/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/28703794/impaired-autophagosome-clearance-contributes-to-neuronal-death-in-a-piglet-model-of-neonatal-hypoxic-ischemic-encephalopathy
#6
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
#7
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/28694354/myocardial-upregulation-of-cathepsin-d-by-ischemic-heart-disease-promotes-autophagic-flux-and-protects-against-cardiac-remodeling-and-heart-failure
#8
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/28692478/diagnosis-of-vitality-in-skin-wounds-in-the-ligature-marks-resulting-from-suicide-hanging
#9
Isabel Legaz Pérez, Maria Falcón, M Gimenez, F Martínez Diaz, M D Pérez-Cárceles, E Osuna, D Nuno-Vieira, A Luna
Ascertaining the vital origin of skin wounds is one of the most challenging problems in forensic pathology. The forensic literature describes biomarkers and methods for differentiating vital and postmortem wounds, although no clear conclusions have been reached. The aim of this study was to characterize human vital wounds by analyzing the concentrations of metallic ions and the expression of P-selectin and cathepsin D in skin wounds in the ligature marks in a cohort of suicidal hangings for which vitality was previously demonstrated...
July 7, 2017: American Journal of Forensic Medicine and Pathology
https://www.readbyqxmd.com/read/28646121/at1-receptor-blockade-attenuates-outward-aortic-remodeling-associated-with-diet-induced-obesity-in-mice
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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