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https://www.readbyqxmd.com/read/27923262/circulating-levels-of-lamp2-in-coronary-artery-disease-association-with-serum-lipid-profile
#1
M Teimouri, P Shabani, F Zali, M Najafi, H Shateri, M Asadnia, A Vatannejad, M Najafi, M Doosti
Whereas several in vitro and in vivo studies have described the role of lysosomal associated membrane protein 2 (LAMP2) in lipid homeostasis, there is no study addressing LAMP2 serum concentration and its association with lipid profiles in the context of coronary artery disease (CAD). We aimed to determine the LAMP2 serum concentration and its association with serum lipid profiles as well as the gene expression of LAMP2 in peripheral blood mononuclear cells (PBMCs) of CAD patients and control group. Circulating levels of LAMP2 were quantified by enzyme-linked immunosorbent assay (ELISA) in CAD patients (n=85) and control group (n=65) and correlation to lipid parameters was assessed...
December 6, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27923041/crystal-structure-of-the-salmonella-typhimurium-effector-gtge
#2
Caishuang Xu, Guennadi Kozlov, Kathy Wong, Kalle Gehring, Miroslaw Cygler
Salmonella Typhimurium GtgE is an effector protein contributing to the virulence of this pathogen. It was shown to possess highly selective proteolytic activity against a subset of Rab proteins that helps in evasion of Salmonella-containing vacuole (SCV) fusion with lysosomes. Cys45, His151 and Asp169 are essential for proteolytic activity. The structure of a C-terminal fragment GtgE(79-214) indicated the presence of a papain-like fold. Here, we present the structure of GtgE(17-214) containing the fully assembled active site...
2016: PloS One
https://www.readbyqxmd.com/read/27922670/downregulation-of-laptm5-suppresses-cell-proliferation-and-viability-inducing-cell-cycle-arrest-at-g0-g1-phase-of-bladder-cancer-cells
#3
Liang Chen, Gang Wang, Yi Luo, Yongzhi Wang, Conghua Xie, Wei Jiang, Yu Xiao, Guofeng Qian, Xinghuan Wang
Our transcriptome analysis revealed in bladder cancer (BCa) tissues a significant induction of lysosomal-associated multispanning membrane protein 5 (LAPTM5), a lysosomal membrane protein preferentially expressing in immune cells and hematopoietic cells. Transportation of LAPTM5 from Golgi to lysosome could be inhibited by deficiency of Nedd4, a key member of E3 ubiquitin ligase family overexpressing in invasive BCa and promoting its progression. Therefore, we hypothesize that LAPTM5 may be closely correlated with BCa tumorigenesis...
December 5, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27922618/macroautophagy-without-lc3-conjugation
#4
Maurizio Renna, David C Rubinsztein
A recent study makes the surprising observation that autophagosomes can still form in the absence of the core conjugation machinery. Furthermore, while such autophagosomes can fuse with lysosomes, their degradation is delayed, and this is associated with delayed destruction of the inner autophagosomal double membrane, highlighting a new role for proteins thought to act exclusively in the formation of autophagosomes in late stages of the autophagic itinerary within autolysosomes.
December 6, 2016: Cell Research
https://www.readbyqxmd.com/read/27922495/toxic-and-endocrine-myopathies
#5
Hans D Katzberg, Charles D Kassardjian
PURPOSE OF REVIEW: This article discusses the clinical features, pathophysiology, and management of toxic and endocrine myopathies. RECENT FINDINGS: Early detection and expeditious correction of metabolic disturbances in endocrinopathies such as Cushing syndrome, thyroid and parathyroid diseases, and acromegaly can minimize and prevent neurologic complications including myopathy. Recently proposed mechanisms of injury in patients with critical illness myopathy include inhibition of protein synthesis, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, oxidative stress, and disruption of intramuscular calcium homeostasis, which can cause a myosin-loss myopathy...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27922193/phagocytosis-of-collagen-fibrils-by-fibroblasts-in-vivo-is-independent-of-the-uparap-endo180-receptor
#6
Sara Sprangers, Niels Behrendt, Lars Engelholm, Yixuan Cao, Vincent Everts
As a crucial step in ECM remodeling, collagen degradation occurs through different processes, including both extracellular and intracellular degradation. The extracellular pathways of collagen degradation require secretion of collagenolytic proteases, whereas intracellular collagen degradation occurs in the lysosomal compartment after uptake, involving either pre-cleaved or intact fibrillar collagen. The endocytic collagen receptor uPARAP/Endo180 plays an important role in internalization of large collagen degradation products, whereas its role in the phagocytosis of fibrillar collagen has been debated...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922190/clc-3-promotes-osteogenic-differentiation-in-mc3t3-e1-cell-after-dynamic-compression
#7
Dawei Wang, Hao Wang, Feng Gao, Kun Wang, Fusheng Dong
ClC-3 chloride channel has been proved to have a relationship with the expression of osteogenic markers during osteogenesis, persistent static compression can upregulate the expression of ClC-3 and regulate osteodifferentiation in osteoblasts. However, there was no study about the relationship between the expression of ClC-3 and osteodifferentiation after dynamic compression. In this study, we applied dynamic compression on MC3T3-E1 cells to detect the expression of ClC-3, runt-related transcription factor 2 (Runx2), bone morphogenic protein-2 (BMP-2), osteopontin (OPN), nuclear-associated antigen Ki67 (Ki67) and proliferating cell nuclear antigen (PCNA) in biopress system, then we investigated the expression of these genes after dynamic compression with Chlorotoxin (specific ClC-3 chloride channel inhibitor) added...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922112/plasma-cathepsin-d-correlates-with-histological-classifications-of-fatty-liver-disease-in-adults-and-responds-to-intervention
#8
Sofie M A Walenbergh, Tom Houben, Sander S Rensen, Veerle Bieghs, Tim Hendrikx, Patrick J van Gorp, Yvonne Oligschlaeger, Mike L J Jeurissen, Marion J J Gijbels, Wim A Buurman, Anita C E Vreugdenhil, Jan Willem M Greve, Jogchum Plat, Marten H Hofker, Satish Kalhan, Jussi Pihlajamäki, Patrick Lindsey, Ger H Koek, Ronit Shiri-Sverdlov
Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920523/pegylated-and-nanoparticle-conjugated-sulfonium-salt-photo-triggers-necrotic-cell-death
#9
Alaa A Fadhel, Xiling Yue, Ebrahim H Ghazvini Zadeh, Mykhailo V Bondar, Kevin D Belfield
Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920219/the-proprotein-convertases-in-hypercholesterolemia-and-cardiovascular-diseases-emphasis-on-proprotein-convertase-subtilisin-kexin-9
#10
REVIEW
Nabil G Seidah, Marianne Abifadel, Stefan Prost, Catherine Boileau, Annik Prat
The secretory proprotein convertase (PC) family comprises nine members, as follows: PC1/3, PC2, furin, PC4, PC5/6, paired basic amino acid cleaving enzyme 4, PC7, subtilisin kexin isozyme 1/site 1 protease (SKI-1/S1P), and PC subtilisin/kexin type 9 (PCSK9). The first seven PCs cleave their substrates at single/paired basic residues and exhibit specific and often essential functions during development and/or in adulthood. The essential SKI-1/S1P cleaves membrane-bound transcription factors at nonbasic residues...
January 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/27919801/folic-acid-capped-pegylated-magnetic-nanoparticles-enter-cancer-cells-mostly-via-clathrin-dependent-endocytosis
#11
Emilie Allard-Vannier, Katel Hervé-Aubert, Karine Kaaki, Thibaut Blondy, Anastasia Shebanova, Konstantin V Shaitan, Anastasia A Ignatova, Marie-Louise Saboungi, Alexey V Feofanov, Igor Chourpa
BACKGROUND: This work is focused on mechanisms of uptake in cancer cells of rationally designed, covalently assembled nanoparticles, made of superparamagnetic iron oxide nanoparticles (SPIONs), fluorophores (doxorubicin or Nile Blue), polyethylene glycol (PEG) and folic acid (FA), referred hereinafter as SFP-FA. METHODS: SFP-FA were characterized by DLS, zetametry and fluorescence spectroscopy. The SFP-FA uptake in cancer cells was monitored using fluorescence-based methods like fluorescence-assisted cell sorting, LSCM with single-photon and two-photon excitation...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27919658/quinolizinium-as-a-new-fluorescent-lysosomotropic-probe
#12
Emmanouil Zacharioudakis, Tatiana Cañeque, Raúl Custodio, Sebastian Müller, Ana M Cuadro, Juan J Vaquero, Raphaël Rodriguez
We have synthesized a collection of quinolizinium fluorescent dyes for the purpose of cell imaging. Preliminary biological studies in human U2OS osteosarcoma cancer cells have shown that different functional groups appended to the cationic quinolizinium scaffold efficiently modulate photophysical properties but also cellular distribution. While quinolizinium probes are known nuclear staining reagents, we have identified a particular quinolizinium derivative salt that targets the lysosomal compartment. This finding raises the question of predictability of specific organelle targeting from structural features of small molecules...
November 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27919184/role-of-engineered-metal-oxide-nanoparticle-agglomeration-in-reactive-oxygen-species-generation-and-cathepsin-b-release-in-nlrp3-inflammasome-activation-and-pulmonary-toxicity
#13
Tina M Sager, Michael Wolfarth, Stephen S Leonard, Anna M Morris, Dale W Porter, Vincent Castranova, Andrij Holian
Incomplete understanding of the contributions of dispersants and engineered nanoparticles/materials (ENM) agglomeration state to biological outcomes presents an obstacle for toxicological studies. Although reactive oxygen species (ROS) production is often regarded as the primary indicator of ENM bioactivity and toxicity, it remains unclear whether ENM produce ROS or whether ROS is an outcome of ENM-induced cell injury. Phagolysosomal disruption and cathepsin B release also promote bioactivity through inflammasome activation...
December 5, 2016: Inhalation Toxicology
https://www.readbyqxmd.com/read/27918488/transcriptome-profiling-analysis-of-wolf-spider-pardosa-pseudoannulata-araneae-lycosidae-after-cadmium-exposure
#14
Chang-Chun Li, Yong Wang, Guo-Yuan Li, Yue-Li Yun, Yu-Jun Dai, Jian Chen, Yu Peng
Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanisms by which spiders respond to heavy metals at the molecular level. In the present study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases...
December 3, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27917893/new-insights-into-molecular-organization-of-human-neuraminidase-1-transmembrane-topology-and-dimerization-ability
#15
Pascal Maurice, Stéphanie Baud, Olga V Bocharova, Eduard V Bocharov, Andrey S Kuznetsov, Charlotte Kawecki, Olivier Bocquet, Beatrice Romier, Laetitia Gorisse, Maxime Ghirardi, Laurent Duca, Sébastien Blaise, Laurent Martiny, Manuel Dauchez, Roman G Efremov, Laurent Debelle
Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139-159 (TM1) and 316-333 (TM2) - as potential transmembrane (TM) domains...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917878/spatiotemporal-control-of-interferon-induced-jak-stat-signalling-and-gene-transcription-by-the-retromer-complex
#16
Daniela Chmiest, Nanaocha Sharma, Natacha Zanin, Christine Viaris de Lesegno, Massiullah Shafaq-Zadah, Vonick Sibut, Florent Dingli, Philippe Hupé, Stephan Wilmes, Jacob Piehler, Damarys Loew, Ludger Johannes, Gideon Schreiber, Christophe Lamaze
Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of the IFNAR complex are differentially sorted by the retromer at the early endosome. Binding of the retromer VPS35 subunit to IFNAR2 results in IFNAR2 recycling to the plasma membrane, whereas IFNAR1 is sorted to the lysosome for degradation...
December 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27917594/a-novel-two-nucleotide-deletion-in-hps6-affects-mepacrine-uptake-and-platelet-dense-granule-secretion-in-a-family-with-hermansky-pudlak-syndrome
#17
Oliver Andres, Verena Wiegering, Eva-Maria König, Anna Lena Schneider, Daniela Semeniak, Simon Stritt, Eva Klopocki, Harald Schulze
BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by oculocutaneous albinism and platelet dysfunction. We report on a novel HPS6 homozygous frameshift variant (c.1919_1920delTC; p.Val640Glyfs*29) in a nonconsanguineous Caucasian family with two affected siblings (index patients) who presented with oculocutaneous albinism at birth and a mild bleeding phenotype during childhood and adolescence. PROCEDURE: Genetic analysis was conducted by panel-based next-generation sequencing (NGS) and Sanger sequencing...
December 4, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27916642/magnetic-hyperthermia-and-ph-responsive-effective-drug-delivery-to-the-sub-cellular-level-of-human-breast-cancer-cells-by-modified-cofe2o4-nanoparticles
#18
Yunok Oh, Madhappan Santha Moorthy, Panchanathan Manivasagan, Subramaniyan Bharathiraja, Junghwan Oh
Magnetic iron oxide nanoparticles (MNPs) have been extensively utilized in a wide range of biomedical applications including magnetic hyperthermia agent. To improve the efficiency of the MNPs in therapeutic applications, in this study, we have synthesized CoFe2O4 nanoparticles and its surface was further functionalized with meso-2,3-dimercaptosuccinic acid (DMSA). The anticancer agent, Doxorubucin (DOX) was conjugated with CoFe2O4@DMSA nanoparticle to evaluate the combined effects of thermotherapy and chemotherapy...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27916601/gaucher-disease-circa-2016-progress-and-ongoing-challenges
#19
REVIEW
Pramod K Mistry, Grisel Lopez, Raphael Schiffmann, Norman W Barton, Neal J Weinreb, Ellen Sidransky
Over the past decades, tremendous progress has been made in the field of Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Many of the colossal achievements took place during the course of the sixty-year tenure of Dr. Roscoe Brady at the National Institutes of Health. These include the recognition of the enzymatic defect involved, the isolation and characterization of the protein, the localization and characterization of the gene and its nearby pseudogene, as well as the identification of the first mutant alleles in patients...
November 17, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27915146/differential-sensitivity-to-cadmium-of-immunomarkers-measured-in-hemocyte-subpopulations-of-zebra-mussel-dreissena-polymorpha
#20
Lauris Evariste, Damien Rioult, Pauline Brousseau, Alain Geffard, Elise David, Michel Auffret, Michel Fournier, Stéphane Betoulle
Increasing discharge of industrial wastes into the environment results in pollution transfer towards hydrosystems. These activities release heavy metals such as cadmium, known as persistent pollutant that is accumulated by molluscs and exercise immunotoxicological effects. Among molluscs, the zebra mussel, Dreissena polymorpha constitutes a suitable support for freshwater ecotoxicological studies. In molluscs, homeostasis maintain is ensured in part by hemocytes that are composed of several cell populations involved in multiple physiological processes such as cell-mediated immune response or metal metabolism...
December 1, 2016: Ecotoxicology and Environmental Safety
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