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cathepsin d

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https://www.readbyqxmd.com/read/29036611/progranulin-mediated-deficiency-of-cathepsin-d-results-in-ftd-and-ncl-like-phenotypes-in-neurons-derived-from-ftd-patients
#1
Clarissa Valdez, Yvette C Wong, Michael Schwake, Guojun Bu, Zbigniew K Wszolek, Dimitri Krainc
Frontotemporal dementia (FTD) encompasses a group of neurodegenerative disorders characterized by cognitive and behavioral impairments. Heterozygous mutations in progranulin (PGRN) cause familial FTD and result in decreased PGRN expression, while homozygous mutations result in complete loss of PGRN expression and lead to the neurodegenerative lysosomal storage disorder neuronal ceroid lipofuscinosis (NCL). However, how dose-dependent PGRN mutations contribute to these two different diseases is not well understood...
September 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29033510/admission-value-of-serum-cathepsin-d-level-can-be-useful-for-predicting-in-hospital-mortality-in-patients-with-nstemi
#2
Harun Kundi, Ahmet Balun, Hulya Cicekcioglu, Mustafa Cetin, Emrullah Kiziltunc, Canan Topcuoglu, Muhammed Fevzi Kilinckaya, Ender Ornek
BACKGROUND: We aimed to investigate the association of serum cathepsin D levels with in-hospital mortality and Syntax scores (SXscore) in non-ST elevation myocardial infarction (NSTEMI) patients. METHODS: A total of 88 patients were included in the study. The patients were divided into two groups: those with in-hospital mortality (-), and those with in-hospital mortality (+). The receiver operating characteristics curve was used to show the sensitivity and specificity of serum cathepsin D levels, and the optimal cut-off value for predicting in-hospital mortality and high SXscore...
July 2017: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/29032300/gastric-cathepsin-d-exception-or-the-rule-in-decapods-crustaceans
#3
Diana Martínez-Alarcón, Reinhard Saborowski, Liliana Rojo-Arreola, Fernando García-Carreño
Cathepsin D is an aspartic endopetidase with typical characteristics of lysosomal enzymes. Cathepsin D activity has been reported in the gastric fluid of clawed lobsters where it acts as an extracellular digestive enzyme. Here we investigate whether cathepsin D is unique in clawed lobsters or, instead, common in decapod crustaceans. Eleven species of decapods belonging to six infraorders were tested for cathepsin D activity in the midgut gland, the muscle tissue, the gills, and when technically possible, in the gastric fluid...
October 11, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29024815/identification-of-a-novel-autophagic-inhibitor-cepharanthine-to-enhance-the-anti-cancer-property-of-dacomitinib-in-non-small-cell-lung-cancer
#4
Zheng-Hai Tang, Wen-Xiang Cao, Xia Guo, Xiao-Yang Dai, Jia-Hong Lu, Xiuping Chen, Hong Zhu, Jin-Jian Lu
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024694/cathepsin-d-non-proteolytically-induces-proliferation-and-migration-in-human-omental-microvascular-endothelial-cells-via-activation-of-the-erk1-2-and-pi3k-akt-pathways
#5
Md Zahidul I Pranjol, Nicholas J Gutowski, Michael Hannemann, Jacqueline L Whatmore
Epithelial ovarian cancer (EOC) frequently metastasises to the omentum, a process that requires pro-angiogenic activation of human omental microvascular endothelial cells (HOMECs) by tumour-secreted factors. We have previously shown that ovarian cancer cells secrete a range of factors that induce pro-angiogenic responses e.g. migration, in HOMECs including the lysosomal protease cathepsin D (CathD). However, the cellular mechanism by which CathD induces these cellular responses is not understood. The aim of this study was to further examine the pro-angiogenic effects of CathD in HOMECs i...
October 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28987802/american-lobster-cathepsin-d-an-aspartic-peptidase-resistant-to-proteolysis-and-active-in-organic-solvents-non-ionic-detergents-and-salts
#6
Ivan Rodriguez-Siordia, Liliana Rojo-Arreola, Maria de Los Angeles Navarrete Del Toro, Fernando García-Carreño
Suitable peptidases for biotechnological applications are those active at low temperature, in organic solvents, detergents or proteolytic additives. American lobster cathepsin D1 (CD1) is an enzyme highly efficient at 5-50°C and at pH 2.5-5.5. We assessed the effect of common industrial additives on CD1 activity. CD1 was isolated from lobster gastric fluid by chromatography. The proteolytic activity was measured using a fluorogenic specific substrate and the conformation by intrinsic fluorescence. Non-ionic detergents Tween-20 and Triton X-100 stabilize the peptidase activity...
October 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28981267/salivary-proteome-patterns-affecting-human-salt-taste-sensitivity
#7
Theresa Stolle, Freya Grondinger, Andreas Dunkel, Chen Meng, Guillaume Médard, Bernhard Kuster, Thomas Hofmann
In order to investigate the role of perireceptor events in inter-individual variability in salt taste sensitivity, 31 volunteers were monitored in their detection functions for sodium chloride (NaCl) and classified into sensitive (0.6 - 1.7 mmol/L), medium sensitive (1.8 - 6.9 mmol/L), and non-sensitive subjects (7.0 - 11.2 mmol/L). Chemosensory intervention of NaCl sensitive (S+) and non-sensitive panellists (S-) with potassium chloride, ammonium chloride, and sodium gluconate, respectively, showed the salt-taste sensitivity to be specific for NaCl...
October 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28978107/foxm1-facilitates-gastric-cancer-cell-migration-and-invasion-by-inducing-cathepsin-d
#8
Li Yang, Ming Cui, Liang Zhang, Lei Song
Forkhead box M1 (FOXM1) has been reported as a vital transcription factor in different human malignancies. To date, the mechanisms of FOXM1 in modulating the invasion and metastasis of gastric cancer cells have not been elucidated. In the present study, we found that overexpression of FOXM1 prompted cell migration and invasion of gastric cancer, and increased the expression of Cathepsin D (Cath-D). However, FOXM1 siRNA repressed cell migration and invasion, and also decreased the expression of Cath-D in gastric cancer cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974016/high-endogenous-accumulation-of-%C3%AF-3-polyunsaturated-fatty-acids-protect-against-ischemia-reperfusion-renal-injury-through-ampk-mediated-autophagy-in-fat-1-mice
#9
Do Hyeong Gwon, Tae Woong Hwang, Ju-Ye Ro, Yoon-Joong Kang, Jin Young Jeong, Do-Kyung Kim, Kyu Lim, Dong Woon Kim, Dae Eun Choi, Jwa-Jin Kim
Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms...
September 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28973941/granulocyte-colony-stimulating-factor-g-csf-signaling-in-spinal-microglia-drives-visceral-sensitization-following-colitis
#10
Lilian Basso, Tamia K Lapointe, Mircea Iftinca, Candace Marsters, Morley D Hollenberg, Deborah M Kurrasch, Christophe Altier
Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28970837/lysosomal-ca-2-signaling-regulates-high-glucose-mediated-interleukin-1%C3%AE-secretion-via-transcription-factor-eb-in-human-monocytic-cells
#11
Hisa Hui Ling Tseng, Chi Teng Vong, Yiu Wa Kwan, Simon Ming-Yuen Lee, Maggie Pui Man Hoi
Aberrant activation of the innate immune system, including NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome-dependent interleukin-1β (IL-1β) secretion, has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and its complication. Our previous study demonstrated that hyperglycemia, a hallmark characteristic of T2DM, induced NLRP3 inflammasome-dependent caspase-1 activation and IL-1β maturation in human monocytic cells. In this study, we examined the underlying mechanisms of secreting IL-1β during hyperglycemia, with a focus on the alteration of Ca(2+) homeostasis and lysosomal exocytosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28968398/snps-near-the-cysteine-proteinase-cathepsin-o-gene-ctso-determine-tamoxifen-sensitivity-in-er%C3%AE-positive-breast-cancer-through-regulation-of-brca1
#12
Junmei Cairns, James N Ingle, Lawrence D Wickerham, Richard Weinshilboum, Mohan Liu, Liewei Wang
Tamoxifen is one of the most commonly employed endocrine therapies for patients with estrogen receptor α (ERα)-positive breast cancer. Unfortunately the clinical benefit is limited due to intrinsic and acquired drug resistance. We previously reported a genome-wide association study that identified common SNPs near the CTSO gene and in ZNF423 associated with development of breast cancer during tamoxifen therapy in the NSABP P-1 and P-2 breast cancer prevention trials. Here, we have investigated their roles in ERα-positive breast cancer growth and tamoxifen response, focusing on the mechanism of CTSO...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28953929/class-ii-and-iv-hdacs-function-as-inhibitors-of-osteoclast-differentiation
#13
Nicholas C Blixt, Bora K Faulkner, Kristina Astleford, Rosemary Lelich, Jacob Schering, Ekaterina Spencer, Rajaram Gopalakrishnan, Eric D Jensen, Kim C Mansky
Histone deacetylases (HDACs) are negative regulators of transcription and have been shown to regulate specific changes in gene expression. In vertebrates, eighteen HDACs have thus far been identified and subdivided into four classes (I-IV). Key roles for several HDACs in bone development and biology have been elucidated through in vitro and in vivo models. By comparison, there is a paucity of data on the roles of individual HDACs in osteoclast formation and function. In this study, we investigated the gene expression patterns and the effects of suppressing individual class II (Hdac4, 5, 6, 9, and 10) and class IV (Hdac11) HDACs during osteoclast differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28945807/modulating-lysosomal-function-through-lysosome-membrane-permeabilization-or-autophagy-suppression-restores-sensitivity-to-cisplatin-in-refractory-non-small-cell-lung-cancer-cells
#14
Magdalena Circu, James Cardelli, Martin Barr, Kenneth O'Byrne, Glenn Mills, Hazem El-Osta
Lung cancer is the leading cause of cancer-related deaths. Most patients develop resistance to platinum within several months of treatment. We investigated whether triggering lysosomal membrane permeabilization (LMP) or suppressing autophagy can restore cisplatin susceptibility in lung cancer with acquired chemoresistance. Cisplatin IC50 in A549Pt (parental) and A549cisR (cisplatin resistant) cells was 13 μM and 47 μM, respectively. Following cisplatin exposure, A549cisR cells failed to elicit an apoptotic response...
2017: PloS One
https://www.readbyqxmd.com/read/28944282/progranulin-acts-as-a-shared-chaperone-and-regulates-multiple-lysosomal-enzymes
#15
Jinlong Jian, Aubryanna Hettinghouse, Chuan-Ju Liu
Multifunctional factor progranulin (PGRN) plays an important role in lysosomes, and its mutations and insufficiency are associated with lysosomal storage diseases, including neuronal ceroid lipofuscinosis and Gaucher disease (GD). The first breakthrough in understanding the molecular mechanisms of PGRN as regulator of lysosomal storage diseases came unexpectedly while investigating the role of PGRN in inflammation. Challenged PGRN null mice displayed typical features of GD. In addition, GRN gene variants were identified in GD patients and the serum levels of PGRN were significantly lower in GD patients...
September 2017: Genes & Diseases
https://www.readbyqxmd.com/read/28942846/trichosporon-asahii-secretes-a-30-kda-aspartic-peptidase
#16
Roberta S Valle, Lívia S Ramos, Vanessa J Reis, Mariangela Ziccardi, Marcos Dornelas-Ribeiro, Cátia L Sodré, Marta H Branquinha, André L S Santos
Trichosporon asahii is a fungal opportunistic pathogen that causes superficial and deep-seated infections presenting high mortality. Very little is known about the virulence attributes produced by this fungus. Herein, aspartic peptidase production was identified in Brazilian clinical isolates of T. asahii by different methodologies. Initially, T. asahii strain 250 (from skin lesion) was inoculated in both liquid and solid culture media containing bovine serum albumin (BSA) as the sole nitrogenous source. A translucent halo around the fungal colony was observed from the 5th day of culture...
December 2017: Microbiological Research
https://www.readbyqxmd.com/read/28942744/biological-function-of-dictyocaulus-viviparus-asparaginyl-peptidase-legumain-1-and-its-suitability-as-a-vaccine-target
#17
Julia Holzhausen, Claas Haake, Sabine Schicht, Petra Hinse, Daniela Jordan, Elisabeth Kremmer, Christina Strube
The present study characterized the biological function of the asparaginyl peptidase legumain-1 (LEG-1) of the bovine lungworm Dictyocaulus viviparus and its suitability as a recombinant vaccine against dictyocaulosis. Quantitative real-time PCR and immunoblot analysis revealed LEG-1 to be almost exclusively transcribed and expressed in parasitic lungworm stages. Immunohistochemistry localized the enzyme in the parasite's gut, which was confirmed by immunoblots detecting LEG-1 in the gut as well as male testes...
September 25, 2017: Parasitology
https://www.readbyqxmd.com/read/28940034/protective-effects-of-chymostatin-on-paraquat-induced-acute-lung-injury-in-mice
#18
Chen Yang, Hong-Wei Song, Wei Liu, Xue-Song Dong, Zhi Liu
This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydrate at 0, 1, 2, 4, 8, 12, 24 and 48 h after treatment administration. Blood samples were collected through cardiac puncture. Lung tissues were stained with haematoxylin and eosin for the observation of lung histology...
September 22, 2017: Inflammation
https://www.readbyqxmd.com/read/28939529/molecular-cloning-and-functional-characterization-of-cathepsin-d-from-sea-cucumber-apostichopus-japonicus
#19
Cuiping Yu, Yue Cha, Fan Wu, Xianbing Xu, Lei Qin, Ming Du
Cathepsin D (CTSD, EC 3.4.23.5) belongs to aspartic protease family, which is located in lysosomes and is distributed in diverse tissues and cells. CTSD has a wide variety of physiological functions, owing to its proteolytic activity in degradating proteins and peptides. In the current study, the full length cDNA of sea cucumber (Apostichopus japonicus) cathepsin D (AjCTSD) was firstly cloned, then the association between AjCTSD and sea cucumber autolysis was investigated. The full length cDNA of AjCTSD was 2896 bp, with an open reading frame (ORF) for 391 amino acids...
September 20, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28927275/proton-coupled-conformational-allostery-modulates-the-inhibitor-selectivity-for-%C3%AE-secretase
#20
Robert C Harris, Cheng-Chieh Tsai, Christopher R Ellis, Jana Shen
Many important pharmaceutical targets, such as aspartyl proteases and kinases, exhibit pH-dependent dynamics, functions and inhibition. Accurate prediction of their binding free energies is challenging because current computational techniques neglect the effects of pH. Here we combine free energy perturbation calculations with continuous constant pH molecular dynamics to explore the selectivity of a small-molecule inhibitor for β-secretase (BACE1), an important drug target for Alzheimer's disease. The calculations predicted identical affinity for BACE1 and the closely related cathepsin D at high pH; however, at pH 4...
September 21, 2017: Journal of Physical Chemistry Letters
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