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Cathepsin G

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https://www.readbyqxmd.com/read/29128403/cln5-is-secreted-and-functions-as-a-glycoside-hydrolase-in-dictyostelium
#1
Robert J Huber, Sabateeshan Mathavarajah
Ceroid lipofuscinosis neuronal 5 (CLN5) is a member of a family of proteins that are linked to neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, known commonly as Batten disease, affects all ages and ethnicities and is currently incurable. The precise function of CLN5, like many of the NCL proteins, remains to be elucidated. In this study, we report the localization, molecular function, and interactome of Cln5, the CLN5 homolog in the social amoeba Dictyostelium discoideum. Residues that are glycosylated in human CLN5 are conserved in the Dictyostelium homolog as are residues that are mutated in patients with CLN5 disease...
November 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29114958/evidence-for-multiple-modes-of-neutrophil-serine-protease-recognition-by-the-eap-family-of-staphylococcal-innate-immune-evasion-proteins
#2
Daphne A C Stapels, Jordan L Woehl, Fin J Milder, Angelino T Tromp, Aernoud A van Batenburg, Wilco C de Graaf, Samuel C Broll, Natalie M White, Suzan H M Rooijakkers, Brian V Geisbrecht
Neutrophils contain high levels of chymotrypsin-like serine proteases (NSPs) within their azurophilic granules that have a multitude of functions within the immune system. In response, the pathogen Staphylococcus aureus has evolved three potent inhibitors (Eap, EapH1, and EapH2) that protect the bacterium as well as several of its secreted virulence factors from the degradative action of NSPs. We previously showed that these so-called EAP domain proteins represent a novel class of NSP inhibitors characterized by a non-covalent inhibitory mechanism and a distinct target specificity profile...
November 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29104112/unclassified-hemangioma-like-renal-cell-carcinoma-a-potential-diagnostic-pitfall
#3
Kanika Taneja, Sohrab Arora, Craig G Rogers, Nilesh S Gupta, Liang Cheng, Sean R Williamson
Recently, rare renal cell carcinomas (RCC) have been reported to closely mimic hemangioma; however, these have been largely recognizable as clear cell RCC. Conversely, true hemangiomas of the kidney are also increasingly recognized. We report a 62-year-old woman who underwent partial nephrectomy for a hemangioma-like RCC without appreciable clear cell morphology. Immunohistochemistry revealed luminal structures that stained positively for cytokeratin (CK), CK7, carbonic anhydrase IX, PAX8, and high molecular weight keratin (HMWK), admixed with a CD34, CD31, and ERG-positive complex network of vessels...
November 2, 2017: Human Pathology
https://www.readbyqxmd.com/read/29096286/effects-of-single-nucleotide-polymorphisms-and-haplotypes-of-the-protein-kinase-amp-activated-non-catalytic-subunit-gamma-3-prkag3-gene-on-production-meat-quality-and-carcass-traits-in-italian-large-white-pigs
#4
Stefania Dall'Olio, Emilio Scotti, Leonardo Nanni Costa, Luca Fontanesi
PRKAG3 is a major gene for meat quality and production in pigs. In this study, we investigated two single nucleotide polymorphisms (SNPs) of the PRKAG3 promoter region (g.-995A>G and g.-311A>G) in 381 pigs of different breeds. Association between these SNPs and three major haplotypes, constructed including other three substitutions (c.89C>A, c.154A>G and c.595G>A) and different traits (meat quality parameters: pH2h, pHu, glycogen and lactate content, glycolytic potential and cathepsin B activity of Semimembranosus muscle; estimated breeding values and random residuals for growth performances and carcass traits) were analysed in 271 Italian Large White performance tested pigs...
September 25, 2017: Meat Science
https://www.readbyqxmd.com/read/29094619/acute-in-vitro-and-in-vivo-toxicity-of-a-commercial-grade-boron-nitride-nanotube-mixture
#5
Vamsi K Kodali, Jenny R Roberts, Mohammad Shoeb, Michael G Wolfarth, Lindsey Bishop, Tracy Eye, Mark Barger, Katherine A Roach, Sherri Friend, Diane Schwegler-Berry, Bean T Chen, Aleksandr Stefaniak, Kevin C Jordan, Roy R Whitney, Dale W Porter, Aaron D Erdely
Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical and thermal properties. Currently, the toxicity profile of this material is largely unknown. Commercial grade BNNTs are composed of a mixture (BNNT-M) of ∼50-60% BNNTs, and ∼40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with commercial grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7)...
October 2017: Nanotoxicology
https://www.readbyqxmd.com/read/29089436/protease-mediated-suppression-of-drg-neuron-excitability-by-commensal-bacteria
#6
Jessica L Sessenwein, Corey C Baker, Sabindra Pradhananga, Megan E Maitland, Elaine O Petrof, Emma Allen-Vercoe, Curtis Noordhof, David E Reed, Stephen J Vanner, Alan E Lomax
Peripheral pain signaling reflects a balance of pro and anti-nociceptive influences; the contribution by the gastrointestinal (GI) microbiota to this balance has received little attention. Disorders such as inflammatory bowel disease and irritable bowel syndrome are associated with exaggerated visceral nociceptive actions that may involve altered microbial signaling, particularly given the evidence for bacterial dysbiosis. Thus, we tested whether a community of commensal GI bacteria derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) can affect the excitability of male mouse dorsal root ganglion (DRG) neurons...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29083488/c-ebp%C3%AE-controls-osteoclast-terminal-differentiation-activation-function-and-postnatal-bone-homeostasis-through-direct-regulation-of-nfatc1
#7
Wei Chen, Guochun Zhu, Jun Tang, Hou-De Zhou, Yi-Ping Li
Osteoclast lineage commitment and differentiation have been studied extensively, although the mechanism by which transcription factor(s) control osteoclast terminal differentiation, activation and function remains unclear. CCAAT/enhancer-binding protein α (C/ebpα) has been reported to be a key regulator of osteoclast cell lineage commitment, yet C/ebpα's roles in osteoclast terminal differentiation, activation and function and bone homeostasis, under physiological or pathological conditions, have not been studied because newborn C/ebpα null mice die within several hours after birth...
October 30, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29077095/caspase-4-activation-by-a-bacterial-surface-protein-is-mediated-by-cathepsin-g-in-human-gingival-fibroblasts
#8
Hye-Kyoung Jun, Young-Jung Jung, Suk Ji, Sun-Jin An, Bong-Kyu Choi
Caspase-4 is an inflammatory caspase; however, its mechanism of activation is poorly understood. In this study, we demonstrate that Td92, a surface protein of the periodontal pathogen Treponema denticola and a homolog of the Treponema pallidum surface protein Tp92, activates caspase-4 and induces pyroptosis in primary cultured human gingival fibroblasts (HGFs) via cathepsin G activation. Cathepsin G inhibition or siRNA knockdown of cathepsin G inhibited Td92-induced caspase-4 activation and cell death. Td92-induced cell death was significantly inhibited by siRNA knockdown of gasdermin D...
October 27, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29064631/ferric-citrate-supplementation-reduces-red-blood-cell-aggregation-and-improves-cd163-macrophage-mediated-hemoglobin-metabolism-in-a-rat-model-of-high-fat-diet-induced-obesity
#9
Ting-Yun Chang, Kai-Li Liu, Cheng Sheng Chang, Chien-Tien Su, Seu-Hwa Chen, Yu-Chieh Lee, Jung-Su Chang
SCOPE: In adults, >90% of the daily iron requirement is derived from macrophage-mediated heme iron recycling from senescent red blood cells (RBCs) or free hemoglobin (Hb). Currently, the effects of pharmacological doses of iron supplementation on RBCs and heme iron recycling in obesity are unclear. METHODS AND RESULTS: Sprague Dawley rats were fed a standard diet or a 50% high-fat diet (HFD) with (0.25, 1, and 2 g of ferric iron/kg diet) or without ferric citrate supplementation for 12 weeks...
October 24, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29046337/cathepsin-b-is-dispensable-for-cellular-processing-of-cathepsin-b-cleavable-antibody-drug-conjugates
#10
Niña G Caculitan, Josefa Dela Cruz Chuh, Yong Ma, Donglu Zhang, Katherine R Kozak, Yichin Liu, Thomas H Pillow, Jack Sadowsky, Tommy K Cheung, Qui Phung, Benjamin Haley, Byoung-Chul Lee, Robert Akita, Mark X Sliwkowski, Andrew G Polson
Antibody-drug conjugates (ADCs) are designed to selectively bind to tumor antigens via the antibody and release their cytotoxic payload upon internalization. Controllable payload release through judicious design of the linker has been an early technological milestone. Here, we examine the effect of the protease-cleavable valine-citrulline (VC(S)) linker on ADC efficacy. The VC(S) linker was designed to be cleaved by cathepsin B, a lysosomal cysteine protease. Surprisingly, suppression of cathepsin B expression via CRISPR-Cas9 gene deletion or shRNA knockdown had no effect on the efficacy of ADCs with VC(S) linkers armed with a monomethyl auristatin E (MMAE) payload...
October 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/29035863/sero-detection-of-toxocara-canis-infection-in-human-with-t-canis-recombinant-arginine-kinase-cathepsin-l-1-and-tes-26-antigens
#11
Anju Varghese, Opinder K Raina, Dinesh Chandra, Bijay R Mirdha, Naresh H Kelawala, Jayesh B Solanki, Niranjan Kumar, Reghu Ravindran, Anandanarayanan Arun, Ajayta Rialch, Hniang Lalrinkima, Rohan N Kelawala, Subhamoy Samanta
Three recombinant antigens viz. arginine kinase, cathepsin L-1 and TES-26 of Toxocara canis were expressed in Escherichia coli and evaluated for their potential in the detection of T. canis larval infection in human in immunoglobulin G-enzyme linked immunosorbent assay (IgG-ELISA). Results of the IgG-ELISA with the above recombinant antigens were confirmed with commercially available IgG detection kit for T. canis infection used as a standard test. All three recombinant antigens were 100% sensitive in the detection of positive cases (n = 6) of T...
December 20, 2017: Acta Parasitologica
https://www.readbyqxmd.com/read/29030565/proteolytic-signatures-define-unique-thrombin-derived-peptides-present-in-human-wound-fluid-in-vivo
#12
Rathi Saravanan, Sunil S Adav, Yeu Khai Choong, Mariena J A van der Plas, Jitka Petrlova, Sven Kjellström, Siu Kwan Sze, Artur Schmidtchen
The disease burden of failing skin repair and non-healing ulcers is extensive. There is an unmet need for new diagnostic approaches to better predict healing activity and wound infection. Uncontrolled and excessive protease activity, of endogenous or bacterial origin, has been described as a major contributor to wound healing impairments. Proteolytic peptide patterns could therefore correlate and "report" healing activity and infection. This work describes a proof of principle delineating a strategy by which peptides from a selected protein, human thrombin, are detected and attributed to proteolytic actions...
October 13, 2017: Scientific Reports
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
#13
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/28988117/mas-related-g-protein-coupled-receptors-and-cowhage-induced-itch
#14
Vemuri B Reddy, Ehsan Azimi, Lei Chu, Ethan A Lerner
Cowhage is routinely used in human studies of histamine-independent itch. As such, it is of interest to understand its mechanism of action. The active component of cowhage is a cysteine protease called mucunain. As serine proteases can activate members of the protease-activated receptor (PAR) family to induce itch and pain, the mechanism of action of mucunain and cathepsin S, a human cysteine protease, were likewise thought to be through activation of PARs. The demonstration that cathepsin S activates members of the Mas-related G-protein coupled receptor family to induce itch led us to evaluate the activity of mucunain on these receptors...
October 4, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28987647/serpin-9-and-13-regulate-hemolymph-proteases-during-immune-responses-of-manduca-sexta
#15
Yan He, Yang Wang, Picheng Zhao, Subrahmanyam Rayaprolu, Xiuhong Wang, Xiaolong Cao, Haobo Jiang
Serpins are a superfamily of proteins, most of which inhibit cognate serine proteases by forming inactive acyl-enzyme complexes. In the tobacco hornworm Manduca sexta, serpin-1, -3 through -7 negatively regulate a hemolymph serine protease system that activates precursors of the serine protease homologs (SPHs), phenoloxidases (POs), Spätzles, and other cytokines. Here we report the cloning and characterization of M. sexta serpin-9 and -13. Serpin-9, a 402-residue protein most similar to Drosophila Spn77Ba, has R(366) at the P1 position right before the cleavage site; Serpin-13, a 444-residue ortholog of Drosophila Spn28Dc, is longer than the other seven serpins and has R(410) as the P1 residue...
November 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28983296/recombinant-trichinella-pseudospiralis-serine-protease-inhibitors-alter-macrophage-polarization-in-vitro
#16
Ning Xu, Xiaolei Liu, Bin Tang, Libo Wang, Hai N Shi, Pascal Boireau, Mingyuan Liu, Xue Bai
During parasite infection, serine protease inhibitors secreted by parasites play important roles in suppressing host defenses. However, the mechanism of immune regulation is unclear. In this study, a serpin gene from Trichinella pseudospiralis, named Tp-Serpin, was cloned and expressed, in order to reveal its role in the regulation of the host immune response in T. pseudospiralis infection. The results showed that Tp-Serpin encodes a 43 kDa protein that was recognized by serum from T. pseudospiralis infected mice at 60 days post-infection (dpi)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28981267/salivary-proteome-patterns-affecting-human-salt-taste-sensitivity
#17
Theresa Stolle, Freya Grondinger, Andreas Dunkel, Chen Meng, Guillaume Médard, Bernhard Kuster, Thomas Hofmann
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 nonsensitive (7.0-11.2 mmol/L) subjects. Chemosensory intervention of NaCl-sensitive (S(+)) and nonsensitive (S(-)) panellists with potassium chloride, ammonium chloride, and sodium gluconate showed the salt taste sensitivity to be specific for NaCl...
October 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28973941/granulocyte-colony-stimulating-factor-g-csf-signaling-in-spinal-microglia-drives-visceral-sensitization-following-colitis
#18
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 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28962123/whole-genome-gene-expression-changes-and-hematological-effects-of-rikkunshito-in-patients-with-advanced-non-small-cell-lung-cancer-receiving-first-line-chemotherapy
#19
Yung-Che Chen, An-Shen Lin, Yu-Chiang Hung, Kuang-Den Chen, Ching-Yuan Wu, Chien-Hao Lie, Chang-Chun Hsiao, Chung-Jen Chen, Shih-Feng Liu, Wen-Feng Fang, Jen-Chieh Chang, Ting-Ya Wang, Yi-Hsi Wang, Yu-Hsiu Chung, Tung-Ying Chao, Sum-Yee Leung, Mao-Chang Su, Meng-Chih Lin
It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28951461/inflammatory-monocytes-promote-perineural-invasion-via-ccl2-mediated-recruitment-and-cathepsin-b-expression
#20
Richard L Bakst, Huizhong Xiong, Chun-Hao Chen, Sylvie Deborde, Anna Lyubchik, Yi Zhou, Shizhi He, William F McNamara, Sei-Young Lee, Oakley C Olson, Ingrid Leiner, Andrea R Marcadis, James W Keith, Hikmat A Al-Ahmadie, Nora Katabi, Ziv Gil, Efsevia Vakiani, Johanna A Joyce, Eric G Pamer, Richard J Wong
Perineural invasion (PNI) is an ominous event strongly linked to poor clinical outcome. Cells residing within peripheral nerves collaborate with cancer cells to enable PNI but the contributing conditions within the tumor microenvironment are not well understood. Here we show that CCR2-expressing inflammatory monocytes (IM) are preferentially recruited to sites of PNI, where they differentiate into macrophages and potentiate nerve invasion through a cathepsin B-mediated process. A series of adoptive transfer experiments with genetically engineered donors and recipients demonstrated that IM recruitment to nerves was driven by CCL2 released from Schwann cells at the site of PNI, but not CCL7, an alternate ligand for CCR2...
September 26, 2017: Cancer Research
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