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cathepsin d

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https://www.readbyqxmd.com/read/29686948/you-can-t-fix-what-isn-t-broken-eight-weeks-of-exercise-do-not-substantially-change-cognitive-function-and-biochemical-markers-in-young-and-healthy-adults
#1
Joanne Gourgouvelis, Paul Yielder, Sandra T Clarke, Hushyar Behbahani, Bernadette Murphy
Objective: The benefits of exercise on brain health is well known in aging and psychiatric populations. However, the relationship between habitual exercise in young and healthy adults remains unclear. This study explored the effects an eight-week exercise prescription on cognitive function, brain-derived neurotrophic factor (BDNF) and cathepsin B (CTHB) in young and healthy adults. Methods: A total of 22 low-active, young and healthy adults were recruited from a local university...
2018: PeerJ
https://www.readbyqxmd.com/read/29679389/down-regulation-of-nramp1-is-associated-with-mptp-mpp-induced-%C3%AE-synuclein-accumulation-and-neurotoxicity
#2
Kuo-Chen Wu, Horng-Huei Liou, Chih-Yu Lee, Chun-Jung Lin
AIMS: The accumulation of α-synuclein is a hallmark in the pathogenesis of Parkinson's disease (PD). Natural resistance-associated macrophage protein-1 (Nramp1) was previously shown to contribute to the degradation of extracellular α-synuclein in microglia under conditions of iron overload. This study was aimed at investigating the role of Nramp1 in α-synuclein pathology in the neuron under MPTP/MPP+ treatment. METHODS: The expression of Nramp1 and pathological features (including iron and α-synuclein accumulation) were examined in the dopaminergic neurons of humans (with and without PD) and of mice (with and without receiving chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication)...
April 21, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29670018/identification-of-placental-aspartic-proteinase-in-the-eurasian-beaver-castor-fiber-l
#3
Aleksandra Lipka, Grzegorz Panasiewicz, Marta Majewska, Lukasz Paukszto, Martyna Bieniek-Kobuszewska, Bozena Szafranska
Aspartic proteinases (AP) form a multigenic group widely distributed in various organisms and includes pepsins (pep), cathepsins D and E, pregnancy associated glycoproteins (PAGs) as well as plant, fungal, and retroviral proteinases. This study describes the transcript identification and expression localization of the AP within the discoid placenta of the Castor fiber . We identified 1257 bp of the AP cDNA sequence, encoding 391 amino acids (aa) of the polypeptide precursor composed of 16 aa signal peptide, 46 aa pro-piece, and 329 aa of the mature protein...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29652546/ataxia-telangiectasia-mutated-kinase-deficiency-impairs-autophagic-response-early-during-myocardial-infarction
#4
Patsy R Thrasher, Stephanie L C Scofield, Suman Dalal, Claire C Crawford, Mahipal Singh, Krishna Singh
Ataxia-telangiectasia mutated kinase (ATM) is activated in response to DNA damage. We have previously shown that ATM plays a critical role in myocyte apoptosis and cardiac remodeling following myocardial infarction (MI). Here, we tested the hypothesis that ATM deficiency results in autophagic impairment in the heart early during MI. MI was induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery (LAD). Structural and biochemical parameters of the heart were measured 4 hours following LAD ligation...
April 13, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29650289/optimization-of-dipeptidic-inhibitors-of-cathepsin-l-for-improved-toxoplasma-gondii-selectivity-and-cns-permeability
#5
Jeffery D Zwicker, Nicolas A Diaz, Alfredo J Guerra, Paul D Kirchhoff, Bo Wen, Duxin Sun, Vern B Carruthers, Scott D Larsen
The neurotropic protozoan Toxoplasma gondii is the second leading cause of death due to foodborne illness in the US, and has been designated as one of five neglected parasitic infections by the Center for Disease Control and Prevention. Currently, no treatment options exist for the chronic dormant-phase Toxoplasma infection in the central nervous system (CNS). T. gondii cathepsin L (TgCPL) has recently been implicated as a novel viable target for the treatment of chronic toxoplasmosis. In this study, we report the first body of SAR work aimed at developing potent inhibitors of TgCPL with selectivity vs the human cathepsin L...
March 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29624112/cathepsin-s-is-associated-with-degradation-of-collagen-i-in-abdominal-aortic-aneurysm
#6
Veronika Klaus, Fadwa Schmies, Christian Reeps, Matthias Trenner, Sarah Geisbüsch, Fabian Lohoefer, Hans-Henning Eckstein, Jaroslav Pelisek
BACKGROUND: Cathepsins have been described in the pathogenesis of abdominal aortic aneurysm (AAA), their exact role, especially in collagen degradation, is still unclear. The aim of the present study was therefore to analyse relevant cathepsins in human AAA tissue samples in relation to collagen I, III, and their degradation products. MATERIALS AND METHODS: Samples from 37 AAA patients obtained from elective open surgical repair and eight healthy non-aneurysmatic aortas from kidney donors were included...
April 6, 2018: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/29616179/expression-and-localization-of-cathepsins-b-d-and-g-in-dupuytren-s-disease
#7
Kirin Tan, Helen D Brasch, Bede van Schaijik, James R Armstrong, Reginald W Marsh, Paul F Davis, Swee T Tan, Tinte Itinteang
Background: The pathogenesis of Dupuytren's disease (DD) remains unclear. An embryonic stem cell (ESC)-like population in the endothelium of the microvessels around tissues that expresses components of the renin-angiotensin system (RAS) has been reported. This study investigated if this primitive population expresses cathepsins B, D, and G, that contribute to RAS bypass loops. Methods: 3,3-Diaminobenzidine immunohistochemical (IHC) staining for cathepsins B, D, and G was performed on sections of formalin-fixed paraffin-embedded DD cords (n = 10) and nodules (n = 10)...
February 2018: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/29613789/design-and-synthesis-of-clinical-candidate-pf-06751979-a-potent-brain-penetrant-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-bace1-inhibitor-lacking-hypopigmentation
#8
Brian T O'Neill, Elizabeth M Beck, Christopher R Butler, Charles E Nolan, Cathleen Gonzales, Lei Zhang, Shawn D Doran, Kimberly Lapham, Leanne M Buzon, Jason K Dutra, Gabriela Barreiro, Xinjun Hou, Luis A Martinez-Alsina, Bruce N Rogers, Anabella Villalobos, John C Murray, Kevin Ogilvie, Erik A LaChapelle, Cheng Chang, Lorraine F Lanyon, Claire M Steppan, Ashley Robshaw, Katherine Hales, Germaine G Boucher, Karamjeet Pandher, Christopher Houle, Claude W Ambroise, David Karanian, David Riddell, Kelly R Bales, Michael A Brodney
A major challenge in the development of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer's disease is the alignment of potency, drug-like properties, and selectivity over related aspartyl proteases such as Cathepsin D (CatD) and BACE2. The potential liabilities of inhibiting BACE2 chronically has only recently begun to emerge as BACE2 impacts the processing of the premelanosome protein (PMEL17) and disrupts melanosome morphology resulting in a depigmentation phenotype...
April 3, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29611199/preliminary-study-of-protein-changes-in-trisomy-21-fetus-by-proteomics-analysis-in-amniocyte
#9
Hui Liu, He Wang, Zhu Hongmei, Haixia Zhang, Shanling Liu
OBJECTIVE: To discover the candidate biomarker proteins of trisomy 21 in amniocytes. METHODS: Amniocentesis was performed to collect AF from women who underwent prenatal diagnosis due to high risk of T21 at 18th -21st week of gestation. Amniocyte samples were collected and karyotyping analysis was used to confirm the chromosomal status (Eighteen samples of T21 amniocytes and twenty samples of chromosomally normal ones). Then backup samples for cytogenetic test were used in this study...
April 2, 2018: Prenatal Diagnosis
https://www.readbyqxmd.com/read/29611115/c-elegans-based-screen-identifies-lysosome-damaging-alkaloids-that-induce-stat3-dependent-lysosomal-cell-death
#10
Yang Li, Yu Zhang, Qiwen Gan, Meng Xu, Xiao Ding, Guihua Tang, Jingjing Liang, Kai Liu, Xuezhao Liu, Xin Wang, Lingli Guo, Zhiyang Gao, Xiaojiang Hao, Chonglin Yang
Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway...
April 2, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29596849/histochemical-characteristics-of-regressing-vessels-in-the-hyaloid-vascular-system-of-neonatal-mice-novel-implication-for-vascular-atrophy
#11
Ayuko Kishimoto, Shunsuke Kimura, Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga, Ah-Mee Park, Toshihiko Iwanaga
The hyaloid vasculature constitutes a transitory system nourishing the internal structures of the developing eye, but the mechanism of vascular regression and its cell biological characteristics are not fully understood. The present study aimed to reveal the specificity of the hyaloid vessels by a systematic immunohistochemical approach for marker substances of myeloid cells and the extracellular matrix (ECM) in neonatal mice. Macrophages immunoreactive for F4/80, cathepsin D, and LYVE-1 gathered around the vasa hyaloidea propria (VHP), while small round cells in vascular lumen of VHP were selectively immunoreactive for galectin-3; their segmented nuclei and immunoreactivities for Ly-6G, CD11b, and myeloperoxidase indicated their neutrophilic origin...
March 26, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29565998/two-key-cathepsins-tgcpb-and-tgcpl-are-targeted-by-the-vinyl-sulfone-inhibitor-k11777-in-in-vitro-and-in-vivo-models-of-toxoplasmosis
#12
Juan D Chaparro, Timmy Cheng, Uyen Phuong Tran, Rosa M Andrade, Sara B T Brenner, Grace Hwang, Shara Cohn, Ken Hirata, James H McKerrow, Sharon L Reed
Although toxoplasmosis is one of the most common parasitic infections worldwide, therapeutic options remain limited. Cathepsins, proteases that play key roles in the pathogenesis of toxoplasmosis and many other protozoan infections, are important potential therapeutic targets. Because both TgCPB and TgCPL play a role in T. gondii invasion, we evaluated the efficacy of the potent, irreversible vinyl sulfone inhibitor, K11777 (N-methyl-piperazine-Phe-homoPhe-vinylsulfone-phenyl). The inhibitor's toxicity and pharmacokinetic profile have been well-studied because of its in vitro and in vivo activity against a number of parasites...
2018: PloS One
https://www.readbyqxmd.com/read/29550006/ovariectomy-exacerbates-apical-periodontitis-in-rats-with-an-increase-in-expression-of-proinflammatory-cytokines-and-matrix-metalloproteinases
#13
Priscilla Coutinho Romualdo, Marília P Lucisano, Francisco Wanderley G Paula-Silva, Graziela B Leoni, Manoel D Sousa-Neto, Raquel Assed B Silva, Lea Assed B Silva, Paulo Nelson-Filho
INTRODUCTION: The aim of this study was to evaluate the gene expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and cathepsin K in apical periodontitis (AP) and the volume of lesions in ovariectomized and sham-operated rats. METHODS: Twenty 12-week-old female Wistar rats were subjected to ovariectomy (OVX) or sham surgery. After 9 weeks, access cavities were prepared in the maxillary and mandibular first molars, pulp tissue was removed, and canals were exposed to the oral environment during 21 days for the induction of AP...
March 14, 2018: Journal of Endodontics
https://www.readbyqxmd.com/read/29546879/cathepsin-d-deficiency-delays-central-nervous-system-myelination-by-inhibiting-proteolipid-protein-trafficking-from-late-endosome-lysosome-to-plasma-membrane
#14
Da-Zhi Guo, Lin Xiao, Yi-Jun Liu, Chen Shen, Hui-Fang Lou, Yan Lv, Shu-Yi Pan
This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells...
March 16, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29522724/long-term-treatment-with-anti-vegf-does-not-induce-cell-aging-in-primary-retinal-pigment-epithelium
#15
Johann Schottler, Niklas Randoll, Ralph Lucius, Amke Caliebe, Johann Roider, Alexa Klettner
Anti-Vascular Endothelial Growth Factor (VEGF) therapy is given repeatedly for an extended period of time to patients when treated for age-related macular degeneration. While short-term effects of anti-VEGF agents on retinal pigment epithelial (RPE) cells have been investigated, the effects of long-term and repeated treatment on these cells are scarce. In this study, we have investigated the effects of anti-VEGF treatment after long-term, repeated treatment on cell aging and morphology. The experiments were conducted in primary porcine RPE cells passage one and two...
March 6, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29510992/loss-of-the-nuclear-pool-of-ubiquitin-ligase-chip-stub1-in-breast-cancer-unleashes-the-mzf1-cathepsin-pro-oncogenic-program
#16
Haitao Luan, Bhopal Mohapatra, Timothy A Bielecki, Insha Mushtaq, Sameer Mirza, Tameka A Jennings, Robert J Clubb, Wei An, Dena Ahmed, Rokaya El Ansari, Matthew D Storck, Nitish K Mishra, Chittibabu Guda, Yuri M Sheinin, Jane L Meza, Srikumar Raja, Emad A Rakha, Vimla Band, Hamid Band
CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss of nuclear but not cytoplasmic CHIP to predict more aggressive tumorigenesis and shorter patient survival, with loss of CHIP in two-thirds of ErbB2+ and triple-negative breast cancers and in one-third of ER+ breast cancers. Reduced CHIP expression was seen in breast cancer patient-derived xenograft tumors and in ErbB2+ and triple-negative breast cancer cell lines...
March 6, 2018: Cancer Research
https://www.readbyqxmd.com/read/29505813/lysosomal-response-in-relation-to-%C3%AE-synuclein-pathology-differs-between-parkinson-s-disease-and-multiple-system-atrophy
#17
Gina Puska, Mirjam I Lutz, Kinga Molnar, Günther Regelsberger, Gerda Ricken, Walter Pirker, Lajos Laszlo, Gabor G Kovacs
Intracellular deposition of pathologically altered α-synuclein mostly in neurons characterises Parkinson's disease (PD), while its accumulation predominantly in oligodendrocytes is a feature of multiple system atrophy (MSA). Recently a prion-like spreading of pathologic α-synuclein has been suggested to play a role in the pathogenesis of PD and MSA. This implicates a role of protein processing systems, including lysosomes, supported also by genetic studies in PD. However, particularly for MSA, the mechanism of cell-to-cell propagation of α-synuclein is yet not fully understood...
March 2, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29501392/cathepsin-d-contributes-to-the-accumulation-of-advanced-glycation-end-products-during-photoaging
#18
Xinya Xu, Yue Zheng, Yunfen Huang, Jian Chen, Zijian Gong, Yuying Li, Chun Lu, Wei Lai, Qingfang Xu
BACKGROUND: The deposition of advanced glycation end products (AGEs) is accelerated in photoaged skin, but the underlying mechanisms remain elusive. Intracellular degradation has been recently considered to play an important role in AGEs removal. Although lysosomal cathepsin D (CatD), B (CatB), L(CatL) and proteasomes are found to degrade internalized AGEs, it remains unknown which protease degrades internalized AGEs in human dermal fibroblasts (HDFs), and whether a decrease in intracellular degradation contributes to enhanced AGEs deposition in photoaged skin...
February 19, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29500339/hydroxychloroquine-attenuates-renal-ischemia-reperfusion-injury-by-inhibiting-cathepsin-mediated-nlrp3-inflammasome-activation
#19
Tao-Tao Tang, Lin-Li Lv, Ming-Ming Pan, Yi Wen, Bin Wang, Zuo-Lin Li, Min Wu, Feng-Mei Wang, Steve D Crowley, Bi-Cheng Liu
Inflammation is a major contributor to the pathogenesis of ischemic acute kidney injury (AKI), which complicates the post-operative outcomes of large numbers of hospitalized surgical patients. Hydroxychloroquine (HCQ), a well-known anti-malarial drug, is commonly used in clinical practice for its anti-inflammatory actions. However, little is known about its role in renal ischemia/reperfusion (I/R) injury. In the current study, mice were subjected to I/R injury and HCQ was administered for seven days by gavage prior to surgery...
March 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29464689/distinction-of-fly-artifacts-from-human-blood-using-immunodetection
#20
David B Rivers, Gillian Acca, Marc Fink, Rebecca Brogan, Dorothy Chen, Andrew Schoeffield
Insect stains produced by necrophagous flies are indistinguishable morphologically from human bloodstains. At present, no diagnostic tests exist to overcome this deficiency. As the first step toward developing a chemical test to recognize fly artifacts, polyclonal antisera were generated in rats against three distinct antigenic sequences of fly cathepsin D-like proteinase, an enzyme that is structurally distinct in cyclorrhaphous Diptera from other animals. The resulting rat antisera bound to artifacts produced by Protophormia terraenovae and synthetic peptides used to generate the polyclonal antisera, but not with any type of mammalian blood tested in immunoassays...
February 21, 2018: Journal of Forensic Sciences
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