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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/29036202/toxoplasma-gondii-induces-fak-src-stat3-signaling-during-infection-of-host-cells-that-prevents-parasite-targeting-by-autophagy
#2
Jose-Andres C Portillo, Luis Muniz-Feliciano, Yalitza Lopez Corcino, So Jung Lee, Jennifer Van Grol, Sarah J Parsons, William P Schiemman, Carlos S Subauste
Targeting of Toxoplasma gondii by autophagy is an effective mechanism by which host cells kill the protozoan. Thus, the parasite must avoid autophagic targeting to survive. Here we show that the mammalian cytoplasmic molecule Focal Adhesion Kinase (FAK) becomes activated during invasion of host cells. Activated FAK appears to accompany the formation of the moving junction (as assessed by expression the parasite protein RON4). FAK activation was inhibited by approaches that impaired β1 and β3 integrin signaling...
October 16, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29035891/inhibiting-ros-tfeb-dependent-autophagy-enhances-salidroside-induced-apoptosis-in-human-chondrosarcoma-cells
#3
Wei Zeng, Tao Xiao, Anlie Cai, Weiliang Cai, Huanhuan Liu, Jingling Liu, Jie Li, Miduo Tan, Li Xie, Ying Liu, Xiangcheng Yang, Yi Long
BACKGROUND/AIMS: Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. METHODS: We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29035746/the-exploration-of-endocytic-mechanisms-of-pla-peg-nanoparticles-prepared-by-coaxialtri-capillary-electrospray-template-removal-method
#4
Jiaming Chen, Lihua Cao, Yuecheng Cui, Kehua Tu, Hongjun Wang, Li-Qun Wang
The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with core-shell structure were efficiently prepared by using coaxial tri-capillary electrospray-template removal method. The cellular uptake mechanism, intracellular distribution and exocytosis in A549 cell model of electrosprayed PLA-PEG nanoparticles were systemically studied. The drug release behavior of electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells...
October 2, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29035561/enhancing-photochemical-internalization-of-dox-through-a-porphyrin-based-amphiphilic-block-copolymer
#5
Jia Tian, Lei Xu, Yudong Xue, Xiaoze Jiang, Weian Zhang
Drug resistance is a primary obstacle that seriously reduces therapy efficiency of most chemotherapeutic agents. To address this issue, the photochemical internalization (PCI) was employed to help the anticancer drug escape from lysosome and improve their translocation to the nucleus. Herein, a pH-sensitive porphyrin-based amphiphilic block copolymer (PEG113-b-PCL54-a-porphyrin) was synthesized, which was acted not only as a carrier for the delivery of DOX, but also as a photosensitizer for PCI.PEG113-b-PCL54-a-porphyrin as a drug carrier exhibited a higher drug loading capacity, entrapment efficiency and DOX release content...
October 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29035377/nme4-nucleoside-diphosphate-kinase-d-in-cardiolipin-signaling-and-mitophagy
#6
Uwe Schlattner, Malgorzata Tokarska-Schlattner, Richard M Epand, Mathieu Boissan, Marie-Lise Lacombe, Valerian E Kagan
Mitophagy is an emerging paradigm for mitochondrial quality control and cell homeostasis. Dysregulation of mitophagy can lead to human pathologies such as neurodegenerative disorders and contributes to the aging process. Complex protein signaling cascades have been described that regulate mitophagy. We have identified a novel lipid signaling pathway that involves the phospholipid cardiolipin (CL). CL is synthesized and normally confined at the inner mitochondrial membrane. However, upon a mitophagic trigger, ie, collapse of the inner membrane potential, CL is rapidly externalized to the mitochondrial surface with the assistance of the hexameric nucleoside diphosphate kinase D (NME4, NDPK-D, or NM23-H4)...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035194/clinicopathologic-characteristics-of-light-chain-proximal-tubulopathy-with-light-chain-inclusions-involving-multiple-renal-cell-types%C3%A2
#7
Xiaomei Li, Feng Xu, Dandan Liang, Shaoshan Liang, Xiaodong Zhu, Mingchao Zhang, Xianghua Huang, Zhihong Liu, Caihong Zeng
Light chain proximal tubulopathy (LCPT) associated with plasma cell dyscrasias is a rare abnormality, especially cases involving multiple cell types. The aim of this study is to explore the characteristics and outcomes of these diseases. We comprehensively evaluated the clinical-pathological data, treatment, and outcomes of 6 LCPT patients with involvement of multiple cell types. In 3 cases, we found that the inclusions largely existed in tubular cells, while in 2 cases they coexisted in podocytes and tubular cells, and in 1 case they coexisted in histiocytes and tubular cells...
October 16, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/29034767/in-search-of-a-converging-cellular-mechanism-in-nanotoxicology-and-nanomedicine-in-the-treatment-of-cancer
#8
Mary Gulumian, Charlene Andraos
Multiple applications of nanomaterials have raised concern with regard to their toxicity. With increasing research into nanomaterial safety, mechanisms involved in the toxic effects of nanomaterials have begun to emerge. The importance of nanomaterial-induced lysosomal membrane permeabilization through overloading or direct damage of the lysosomal compartment, resulting in the blockade of autophagosome-lysosome fusion and autophagy dysfunction, as well as inflammasome activation were cited as emerging mechanisms of nanomaterial toxicity...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29034085/amp-activated-protein-kinase-not-just-an-energy-sensor
#9
REVIEW
David Grahame Hardie, Sheng-Cai Lin
Orthologues of AMP-activated protein kinase (AMPK) occur in essentially all eukaryotes as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits. The canonical role of AMPK is as an energy sensor, monitoring levels of the nucleotides AMP, ADP, and ATP that bind competitively to the γ subunit. Once activated, AMPK acts to restore energy homeostasis by switching on alternate ATP-generating catabolic pathways while switching off ATP-consuming anabolic pathways. However, its ancestral role in unicellular eukaryotes may have been in sensing of glucose rather than energy...
2017: F1000Research
https://www.readbyqxmd.com/read/29033400/protective-effects-of-luteolin-7-o-glucoside-against-starvation-induced-injury-through-upregulation-of-autophagy-in-h9c2-cells
#10
Hong Yao, Lichun Zhou, Linlin Tang, Yanhui Guan, Shang Chen, Yu Zhang, Xiuzhen Han
Cardiomyocyte nutrient deprivation is a common clinical event that mediates various cardiac ischemic processes and is associated with autophagy activation and cell survival or death. Luteolin-7-O-glucoside (LUTG) was one of the flavonoid glycosides isolated from Dracocephalum tanguticum. Previous research had showed that LUTG pretreatment had significant protective effects against doxorubicin-induced cardiotoxicity. However, whether LUTG could protect cardiomyocytes from starvation-induced injury was not clear...
October 16, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/29033128/the-dna-inflammasome-in-human-myeloid-cells-is-initiated-by-a-sting-cell-death-program-upstream-of-nlrp3
#11
Moritz M Gaidt, Thomas S Ebert, Dhruv Chauhan, Katharina Ramshorn, Francesca Pinci, Sarah Zuber, Fionan O'Duill, Jonathan L Schmid-Burgk, Florian Hoss, Raymund Buhmann, Georg Wittmann, Eicke Latz, Marion Subklewe, Veit Hornung
Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3...
October 7, 2017: Cell
https://www.readbyqxmd.com/read/29033105/public-attitudes-toward-expanded-newborn-screening
#12
Jane M DeLuca
PURPOSE: There is limited research available on public knowledge and understanding of expanded newborn screening (NBS). The aims of this study were to assess current public knowledge and understanding of newborn screening disorders and procedures, perceived education needs, and preferences for the delivery of NBS information and education. An additional aim was to develop a beginning understanding of public attitudes toward screening for complex, severe, and in some cases untreatable disorders...
October 12, 2017: Journal of Pediatric Nursing
https://www.readbyqxmd.com/read/29032941/ferritin-iron-regulators-pcbp1-and-ncoa4-respond-to-cellular-iron-status-in-developing-red-cells
#13
Moon-Suhn Ryu, Kari A Duck, Caroline C Philpott
Developing red blood cells exhibit multiple, redundant systems for regulating and coordinating the uptake of iron, the synthesis of heme, and the formation of hemoglobin during terminal differentiation. We recently described the roles of poly rC-binding protein (PCBP1) and nuclear coactivator 4 (NCOA4) in mediating the flux of iron through ferritin in developing erythroid cells, with PCBP1, an iron chaperone, delivering iron to ferritin and NCOA4, an autophagic cargo receptor, directing ferritin to the lysosome for degradation and iron release...
September 28, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29032356/cell-scientist-to-watch-mahak-sharma
#14
(no author information available yet)
Mahak Sharma graduated with a bachelor's degree in biotechnology from the Guru Gobind Singh Indraprastha University, Delhi, India. She then moved to the laboratory of Steve Caplan at the University of Nebraska Medical Center, Omaha, USA, where she received her PhD in 2009. After post-doctoral research with Michael Brenner at the Department of Rheumatology, Immunology and Allergy at Harvard Medical School, she returned to India in 2011 as an Assistant Professor at the Indian Institute of Science, Education and Research (IISER) in Mohali...
October 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29032300/gastric-cathepsin-d-exception-or-the-rule-in-decapods-crustaceans
#15
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/29032143/effects-of-cr-vi-on-ca-2-atpase-activity-in-the-earthworm-eisenia-andrei
#16
Marta Boeri, Caterina Oliveri, Corrado Camurati, Aldo Viarengo, Susanna Sforzini
The effect of Cr(VI) as a soil contaminant on the edaphic worm Eisenia andrei was studied by evaluating the activity of Ca(2+)-ATPase in the intestinal mucosa. In eukaryotes, Ca(2+)-ATPase is a key mediator of cell signaling although comparatively little is known about its activity in earthworms. Size and anatomical constraints (i.e. small and complex) led us to develop and optimize a cyto-biochemical method to measure Ca(2+)-ATPase activity in earthworms. The principal site of enzyme activity was found to be the post clitellar intestinal tract; immunohistochemistry then identified plasma membrane Ca(2+)-ATPase (PMCA ATPase) in the apical area of the intestinal epithelium...
October 11, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29031718/g%C3%AE-s-regulates-glucagon-like-peptide-1-receptor-mediated-cyclic-amp-generation-at%C3%A2-rab5-endosomal-compartment
#17
Shravan Babu Girada, Ramya S Kuna, Shilpak Bele, Zhimeng Zhu, N R Chakravarthi, Richard D DiMarchi, Prasenjit Mitra
OBJECTIVE: Upon activation, G protein coupled receptors (GPCRs) associate with heterotrimeric G proteins at the plasma membrane to initiate second messenger signaling. Subsequently, the activated receptor experiences desensitization, internalization, and recycling back to the plasma membrane, or it undergoes lysosomal degradation. Recent reports highlight specific cases of persistent cyclic AMP generation by internalized GPCRs, although the functional significance and mechanistic details remain to be defined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031494/nb-06-from-a-simple-lysosomotropic-asmase-inhibitor-to-tools-for-elucidating-the-role-of-lysosomes-in-signaling-apoptosis-and-lps-induced-inflammation
#18
Markus Blaess, Nelly Bibak, Ralf A Claus, Matthias Kohl, Gabriel A Bonaterra, Ralf Kinscherf, Stefan Laufer, Hans-Peter Deigner
Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli-induced increase of C16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis...
September 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031482/toxicologic-transport-properties-of-ncs-382-a-%C3%AE-hydroxybutyrate-ghb-receptor-ligand-in-neuronal-and-epithelial-cells-therapeutic-implications-for-ssadh-deficiency-a-gaba-metabolic-disorder
#19
K R Vogel, G R Ainslie, A McConnell, J-B Roullet, K M Gibson
We report the in vitro assessment of pharmacotoxicity for the high-affinity GHB receptor ligand, NCS-382, using neuronal stem cells derived from mice with a targeted deletion of the aldehyde dehydrogenase 5a1 gene (succinic semialdehyde dehydrogenase(SSADH)-deficient mice). These animals represent a phenocopy of the human disorder of GABA metabolism, SSADH deficiency, that metabolically features accumulation of both GABA and the GABA-analog γ-hydroxybutyric acid in conjunction with a nonspecific neurological phenotype...
October 11, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29031206/inhibitory-effect-of-triperygium-wilfordii-polyglucoside-on-dipeptidyl-peptidase-i-in-vivo-and-in-vitro
#20
Jingjing Wang, Yi Chu, Xiaoying Zhou
BACKGROUD: Dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease is derived from granule immune cells including mast cell, neutrophils, and toxicity T cells. DPPI can activate serine proteases by removal of dipeptides from N-termini of the pro-proteases, resulting in granule immune cells activation which involved in physiological or pathological responses. Triperygium Wilfordii Polyglucoside (TWP) is one of the traditional Chinese medicines, and commonly used in rheumatoid arthritis (RA) treatment...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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