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https://www.readbyqxmd.com/read/28737711/the-effects-of-artemisinin-on-the-cytolytic-activity-of-natural-killer-nk-cells
#1
Youn Kyung Houh, Kyung Eun Kim, Sunyoung Park, Dae Young Hur, Seonghan Kim, Daejin Kim, Sa Ik Bang, Yoolhee Yang, Hyun Jeong Park, Daeho Cho
Artemisinin, a chemical compound used for the treatment of malaria, has been known to show anti-cancer activity. However, the effect of this chemical on natural killer (NK) cells, which are involved in tumor killing, remains unknown. Here, we demonstrate that artemisinin exerts a potent anti-cancer effect by activating NK cells. NK-92MI cells pre-treated with artemisinin were subjected to a cytotoxicity assay using K562 cells. The results showed that artemisinin significantly enhances the cytolytic activity of NK cells in a dose-dependent manner...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28733901/current-knowledge-on-exosome-biogenesis-and-release
#2
REVIEW
Nina Pettersen Hessvik, Alicia Llorente
Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis...
July 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28731156/protein-interacting-with-c%C3%A2-kinase-1-modulates-exocytosis-and-katp-conductance-in-pancreatic-%C3%AE-cells
#3
Yunhong Li, Fan Li, Bin Bai, Zhenyong Wu, Xiaolin Hou, Ying Shen, Yin Wang
It has been previously identified that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are expressed in pancreatic β cells and regulate exocytosis and insulin release. It is known that protein interacting with C‑kinase 1 (PICK1) regulates trafficking and synaptic targeting of AMPARs in the central nervous system. However, it is unknown whether PICK1 regulates glutamate‑induced insulin release in β cells. The present study demonstrated that glutamate‑induced exocytosis was increased in β cells derived from PICK1‑knockout mice...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28729700/sphingomimetic-multiple-sclerosis-drug-fty720-activates-vesicular-synaptobrevin-and-augments-neuroendocrine-secretion
#4
Frederic D Darios, Jernej Jorgacevski, Ajda Flašker, Robert Zorec, Virginia García-Martinez, José Villanueva, Luis M Gutiérrez, Charlotte Leese, Manjot Bal, Elena Nosyreva, Ege T Kavalali, Bazbek Davletov
Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724787/disrupted-apical-exocytosis-of-cargo-vesicles-causes-enteropathy-in-fhl5-patients-with-munc18-2-mutations
#5
Georg F Vogel, Jorik M van Rijn, Iris M Krainer, Andreas R Janecke, Carsten Posovzsky, Marta Cohen, Claire Searle, Prevost Jantchou, Johanna C Escher, Natalie Patey, Ernest Cutz, Thomas Müller, Sabine Middendorp, Michael W Hess, Lukas A Huber
Familial hemophagocytic lymphohistiocytosis 5 (FHL5) is an autosomal recessive disease caused by mutations in STXBP2, coding for Munc18-2, which is required for SNARE-mediated membrane fusion. FHL5 causes hematologic and gastrointestinal symptoms characterized by chronic enteropathy that is reminiscent of microvillus inclusion disease (MVID). However, the molecular pathophysiology of FHL5-associated diarrhea is poorly understood. Five FHL5 patients, including four previously unreported patients, were studied...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28713781/the-metalloprotease-mpr1-engages-annexina2-to-promote-the-transcytosis-of-fungal-cells-across-the-blood-brain-barrier
#6
Sarisa Na Pombejra, Michelle Salemi, Brett S Phinney, Angie Gelli
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28711685/misunderstandings-and-controversies-about-the-insulin-secreting-properties-of-antidiabetic-sulfonylureas
#7
REVIEW
Jean-Claude Henquin
After 60 years of use in the treatment of type 2 diabetes, hypoglycemic sulfonylureas remain a recommended option in current therapeutic charts. Their binding to sulfonylurea receptor-1, the regulatory subunit of ATP-sensitive potassium channels in the plasma membrane of pancreatic β-cells, leads to closure of the channels, membrane depolarization and influx of Ca(2+) through voltage-gated calcium channels. The resulting increase in cytosolic Ca(2+) triggers exocytosis of insulin granules. Sulfonylureas and glucose thus produce the same triggering signal but, unlike sulfonylureas, glucose does so via acceleration of β-cell metabolism...
July 12, 2017: Biochimie
https://www.readbyqxmd.com/read/28701482/analysis-of-rim-expression-and-function-at-mouse-photoreceptor-ribbon-synapses
#8
Martina Löhner, Norbert Babai, Tanja Müller, Kaspar Gierke, Jenny Atorf, Anneka Joachimsthaler, Angela Peukert, Henrik Martens, Andreas Feigenspan, Jan Kremers, Susanne Schoch, Johann Helmut Brandstätter, Hanna Regus-Leidig
RIM (RAB3A-interacting molecule) proteins are important regulators of transmitter release from active zones. At conventional chemical synapses, RIMs contribute substantially to vesicle priming and docking, and their loss reduces the readily releasable pool of synaptic vesicles by up to 75 %. The priming function of RIMs is mediated via the formation of a tripartite complex with Munc13 and RAB3A, which brings synaptic vesicles in close proximity to Ca(2+) channels and the fusion site, and activates Munc13. We reported previously that at mouse photoreceptor ribbon synapses vesicle priming is Munc13-independent...
July 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28701345/trim9-dependent-ubiquitination-of-dcc-constrains-kinase-signaling-exocytosis-and-axon-branching
#9
Melissa Plooster, Shalini Menon, Cortney C Winkle, Fabio L Urbina, Caroline Monkiewicz, Kristen D Phend, Richard J Weinberg, Stephanie L Gupton
Extracellular netrin-1 and its receptor DCC promote axon branching in developing cortical neurons. Netrin-dependent morphogenesis is preceded by multimerization of DCC, activation of FAK and Src family kinases, and increases in exocytic vesicle fusion, yet how these occurrences are linked is unknown. Here we demonstrate that TRIM9-dependent ubiquitination of DCC blocks the interaction with and phosphorylation of FAK. Upon netrin-1 stimulation TRIM9 promotes DCC multimerization, but TRIM9-dependent ubiquitination of DCC is reduced, which promotes an interaction with FAK and subsequent FAK activation...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28701048/an-overview-of-nanosomes-delivery-mechanisms-trafficking-orders-barriers-and-cellular-effects
#10
Gamaleldin I Harisa, Mohamed M Badran, Fars K Alanazi, Sabry M Attia
This review traces the journey of nanosomes from administration until elimination, and discusses various biological barriers. The nanosomes are imported into the body through different routes and are localized into specified organ, cell, subcellular locations or organelle compartment. The nanosomes delivery to a specific destination depends on the surface chemistry, size, shape and the presence of specific ligands. Endocytosis/exocytosis cycles are involved in the import and export of the nanosomes. The mononuclear phagocytic system and ATP-binding cassette are universal checkpoints for nanosomes trafficking...
July 13, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28698570/exo70-is-an-independent-prognostic-factor-in-colon-cancer
#11
Li Xiao, Kaifeng Zheng, Xia Lv, Jihuan Hou, Liang Xu, Yujie Zhao, Fei Song, Yaqiong Fan, Hanwei Cao, Wenqing Zhang, Xiaoting Hong, Yan-Yan Zhan, Tianhui Hu
Exo70, a key component of the Exocyst complex, plays important roles in human cancer progression beyond exocytosis. However, the expression of Exo70 and its prognostic value for patients with colon cancer has not been well investigated to date. In this study, we observed that the mRNA and protein levels of Exo70 were upregulated in 11 of 13 colon cancer tissues, compared with their normal counterparts, which was validated by immunohistochemical analysis in a tissue microarray containing 89 pairs of colon cancer tissues and the matched adjacent normal tissues...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696682/homogeneous-assays-of-second-messenger-signaling-and-hormone-secretion-using-thermofluorimetric-methods-that-minimize-calibration-burden
#12
Juan Hu, Christopher J Easley
Homogeneous assays are characterized by rapidity, low cost, and simple workflows. However, relatively few specialized homogeneous platforms have garnered significant use in biological studies. Inconsistencies in matrix interferences, limited multiplexability, and the requirement for specialized instrumentation are among the various reasons for delayed acceptance. Recently, we have shown that DNA-driven protein assays using thermofluorimetric analysis (TFA) can limit matrix interference and promote multiplexing, all while requiring only a standard qPCR instrument for readout...
July 11, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28696301/otoferlin-is-a-multivalent-calcium-sensitive-scaffold-linking-snares-and-calcium-channels
#13
Nicole Hams, Murugesh Padmanarayana, Weihong Qiu, Colin P Johnson
Sensory hair cells rely on otoferlin as the calcium sensor for exocytosis and encoding of sound preferentially over the neuronal calcium sensor synaptotagmin. Although it is established that synaptotagmin cannot rescue the otoferlin KO phenotype, the large size and low solubility of otoferlin have prohibited direct biochemical comparisons that could establish functional differences between these two proteins. To address this challenge, we have developed a single-molecule colocalization binding titration assay (smCoBRA) that can quantitatively characterize full-length otoferlin from mammalian cell lysate...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28691876/-physiological-pathophysiological-and-clinical-significance-of-chromogranins-secretogranins
#14
Lajos Jakab
This paper investigates the fundamental knowledge, build-up, as well as essential structural and important features of the big family of chromogranins/secretogranins. Previously the different properties and the slightly diverging funcional relations of the two family members were in focus. Later on, it has been discovered that they are essentially two similar compounds with identical structures and functions, and they are chemically, biochemically related. From details discovered so far we can tell that they are long polypeptid chains formed from amino acids...
July 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28687662/virus-triggered-atp-release-limits-viral-replication-through-facilitating-ifn-%C3%AE-production-in-a-p2x7-dependent-manner
#15
Chengfei Zhang, Hongwang He, Li Wang, Na Zhang, Hongjun Huang, Qingqing Xiong, Yan Yan, Nannan Wu, Hua Ren, Honghui Han, Mingyao Liu, Min Qian, Bing Du
Accumulating evidence shows that innate immune responses are associated with extracellular nucleotides, particularly ATP. In this article, we demonstrate extensive protection of ATP/P2X7 signaling in a host against viral infection. Interestingly, we observed a significant increase in ATP as a danger signal in vesicular stomatitis virus (VSV)-infected cell supernatant and VSV-infected mice in an exocytosis- and pannexin channel-dependent manner. Furthermore, extracellular ATP reduces the replication of VSV, Newcastle disease virus, murine leukemia virus, and HSV in vivo and in vitro through the P2X7 receptor...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28687622/polyphosphate-as-donor-of-high-energy-phosphate-for-the-synthesis-of-adp-and-atp
#16
Werner E G Müller, Shunfeng Wang, Meik Neufurth, Maria Kokkinopoulou, Qingling Feng, Heinz C Schröder, Xiaohong Wang
We studied the potential role of inorganic polyphosphate (polyP) as an energy source for ADP and ATP formation in the extracellular space. Using SaOS-2 we show that matrix vesicles are released into the extracellular space after incubation with polyP. These vesicles contain both the alkaline phosphatase (ALP) and the adenylate kinase (AK). Both enzymes translocate to the cell membrane in response to polyP. To distinguish the process(es) (i) AMP and ADP formation during ALP hydrolysis, from the (ii) ATP generation via the AK reaction, inhibition studies with the AK inhibitor A(5')P5(5')A were performed...
July 7, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28687607/synaptotagmin-isoforms-confer-distinct-activation-kinetics-and-dynamics-to-chromaffin-cell-granules
#17
Tejeshwar C Rao, Zuleirys Santana Rodriguez, Mazdak M Bradberry, Alexandra H Ranski, Peter J Dahl, Michael W Schmidtke, Paul M Jenkins, Daniel Axelrod, Edwin R Chapman, David R Giovannucci, Arun Anantharam
Adrenomedullary chromaffin cells respond to sympathetic nervous system activation by secreting a cocktail of potent neuropeptides and hormones into the circulation. The distinct phases of the chromaffin cell secretory response have been attributed to the progressive fusion of distinct populations of dense core granules with different activation kinetics. However, it has been difficult to define what distinguishes these populations at the molecular level. Functional segregation of granule pools may depend on selective sorting of synaptotagmin-1 (Syt-1) and synaptotagmin-7 (Syt-7), which our previous work showed are rarely cosorted to the same granule...
July 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28686803/the-calcium-sensor-synaptotagmin-1-is-expressed-and-regulated-in-hippocampal-postsynaptic-spines
#18
Suleman Hussain, Daniel Lawer Egbenya, Yi-Chen Lai, Zita J Dosa, Jakob B Sørensen, Anne Anderson, Svend Davanger
Synaptotagmin 1 is a presynaptic calcium sensor, regulating SNARE-mediated vesicle exocytosis of transmitter. Increasing evidence indicate roles of SNARE proteins in postsynaptic glutamate receptor trafficking. However, a possible postsynaptic expression of synaptotagmin 1 has not been demonstrated previously. Here, we used postembedding immunogold electron microscopy to determine the subsynaptic localization of synaptotagmin 1 in rat hippocampal CA1 Schaffer collateral synapses. We report for the first time that synaptotagmin 1 is present in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the postsynaptic density (PSD)...
July 7, 2017: Hippocampus
https://www.readbyqxmd.com/read/28684288/extracellular-vesicles-in-lung-disease
#19
REVIEW
Hiroshi Kubo
Accumulating evidence suggests that extracellular vesicles (EVs) play a role in the pathogenesis of lung diseases. These vesicles include exosomes, ectosomes (ie, microparticles, extracellular vesicles, microvesicles, and shedding vesicles), and apoptotic bodies. Exosomes are generated by inward budding of the membrane (endocytosis), subsequent forming of multivesicular bodies, and release by exocytosis. Ectosomes are formed by outward blebbing from the plasma membrane and are then released by proteolytic cleavage from the cell surface...
July 3, 2017: Chest
https://www.readbyqxmd.com/read/28680752/oral-il-10-suppresses-colon-carcinogenesis-via-elimination-of-pathogeniccd4-t-cells-and-induction-of-antitumor-cd8-t-cell-activity
#20
Tao Gu, Magdia De Jesus, Heather C Gallagher, Thomas P Burris, Nejat K Egilmez
An oral sustained-release formulation of Interleukin-10 suppressed tumor growth and enhanced survival in the APC(min/+)/Bacteroides fragilis spontaneous colon cancer model. Therapeutic benefit was associated with a 5-fold reduction in CD4(+)RORγt(+)Foxp3(-)IL-17(+) T-helper cell, CD4(+)RORγt(+)Foxp3(+)IL-17(+) pathogenic T-regulatory cell and CD4(+)RORγt(-)Foxp3(+)IL-17(-) conventional T-regulatory cell numbers and a concurrent 2-fold enhancement in CD8(+) T-cell activity in the colon. Selective subset depletion and functional blockade studies demonstrated that at steady-state CD4(+)RORγt(+)IL-17(+) T-cell subsets and CD4(+)Foxp3(+) cTreg supported tumorigenesis, whereas CD8(+) cytotoxic T-lymphocytes impeded tumor progression following IL-10 therapy...
2017: Oncoimmunology
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