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https://www.readbyqxmd.com/read/28550810/rigid-aromatic-linking-moiety-in-cationic-lipids-for-enhanced-gene-transfection-efficiency
#1
Bing Wang, Rui-Mo Zhao, Ji Zhang, Yan-Hong Liu, Zheng Huang, Qing-Ying Yu, Xiao-Qi Yu
Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines...
May 17, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28550201/the-influence-of-mhc-class-ii-on-b-cell-defects-induced-by-invariant-chain-cd74-n-terminal-fragments
#2
Janna Schneppenheim, Ann-Christine Loock, Susann Hüttl, Michaela Schweizer, Renate Lüllmann-Rauch, Hans-Heinrich Oberg, Philipp Arnold, Christian H K Lehmann, Diana Dudziak, Dieter Kabelitz, Ralph Lucius, Ana-Maria Lennon-Duménil, Paul Saftig, Bernd Schröder
The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a(-/-) B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550115/involvement-of-cell-surface-90-kda-heat-shock-protein-hsp90-in-pattern-recognition-by-human-monocyte-derived-macrophages
#3
Małgorzata Bzowska, Anna Nogieć, Krystian Bania, Magdalena Zygmunt, Mirosław Zarębski, Jerzy Dobrucki, Krzysztof Guzik
Heat shock proteins (HSPs) are typical intracellular chaperones which also appear on the cell surface and in extracellular milieu. HSP90, which chaperones many proteins involved in signal transduction, is also a regular component of LPS-signaling complexes on Mϕ. As LPS is a prototypical PAMP, we speculated that HSP90 is engaged in pattern recognition by professional phagocytes. In this report, we provide the first evidence, to our knowledge, of the geldanamycin (Ge)-inhibitable HSP90 on the surface of live monocyte-derived Mϕs (hMDMs)...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550045/pacsin2-accelerates-nephrin-trafficking-and-is-up-regulated-in-diabetic-kidney-disease
#4
Vincent Dumont, Tuomas A Tolvanen, Sara Kuusela, Hong Wang, Tuula A Nyman, Sonja Lindfors, Jukka Tienari, Harry Nisen, Shiro Suetsugu, Markus Plomann, Hiroshi Kawachi, Sanna Lehtonen
Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker Diabetic Fatty (ZDF) rats that have altered renal function...
May 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28549840/phosphatidylinositol-4-5-bisphosphate-mediated-pathophysiological-effect-of-hiv-1-tat-protein
#5
REVIEW
Bruno Beaumelle, Petra Tóth, Olfat A Malak, Christophe Chopard, Gildas Loussouarn, Nicolas Vitale
Human immunodeficiency virus (HIV)-infected cells actively release the transcriptional activator (Tat) viral protein that is required for efficient HIV gene transcription. Extracellular Tat is able to enter uninfected cells. We recently reported that internalized Tat escapes endosomes to reach the cytosol and is then recruited to the plasma membrane by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As a consequence, Tat strongly impairs different critical cellular functions in several cell types. Here we will review recent evidences showing that Tat, by affecting the interaction of key cellular effectors with PtdIns(4,5)P2, blocks exocytosis from neuroendocrine cells, perturbs the synaptic vesicle exo-endocytosis cycle, prevents efficient phagocytosis by macrophages, and alters potassium channel activity in cardiac cells...
May 23, 2017: Biochimie
https://www.readbyqxmd.com/read/28548877/role-of-osgin1-in-mediating-smoking-induced-autophagy-in-the-human-airway-epithelium
#6
Guoqing Wang, Haixia Zhou, Yael Strulovici-Barel, Mohammed Al-Hijji, Xuemei Ou, Jacqueline Salit, Matthew S Walters, Michelle R Staudt, Robert J Kaner, Ronald G Crystal
Enhanced macroautophagy/autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the airway epithelium to identify smoking upregulated genes known to respond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 (oxidative stress induced growth inhibitor 1) as significantly upregulated by smoking, in both the large and small airway epithelium, an observation confirmed by an independent small airway microarray cohort, TaqMan PCR of large and small airway samples and RNA-Seq of small airway samples...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28548464/control-of-cell-death-and-mitochondrial-fission-by-erk1-2-map-kinase-signalling
#7
REVIEW
Simon J Cook, Kate Stuart, Rebecca Gilley, Matthew J Sale
The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions...
May 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28547526/rab21-a-novel-ps1-interactor-regulates-%C3%AE-secretase-activity-via-ps1-subcellular-distribution
#8
Zhenzhen Sun, Yujie Xie, Yintong Chen, Qinghu Yang, Zhenzhen Quan, Rongji Dai, Hong Qing
γ-Secretase has been a therapeutical target for its key role in cleaving APP to generate β-amyloid (Aβ), the primary constituents of senile plaques and a hallmark of Alzheimer's disease (AD) pathology. Recently, γ-secretase-associating proteins showed promising role in specifically modulating APP processing while sparing Notch signaling; however, the underlying mechanism is still unclear. A co-immunoprecipitation (Co-IP) coupled with mass spectrometry proteomic assay for Presenilin1 (PS1, the catalytic subunit of γ-secretase) was firstly conducted to find more γ-secretase-associating proteins...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28546219/inos-derived-nitric-oxide-induces-integrin-linked-kinase-endocytic-lysosome-mediated-degradation-in-the-vascular-endothelium
#9
Paula Reventun, Matilde Alique, Irene Cuadrado, Susana Marquez, Rocio Toro, Carlos Zaragoza, Marta Saura
OBJECTIVE: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. APPROACH AND RESULTS: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with inducible NO synthase knockout mice...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28545680/a-role-for-tropomyosins-in-activity-dependent-bulk-endocytosis
#10
REVIEW
R S Gormal, N Valmas, T Fath, F A Meunier
Bulk endocytosis allows stimulated neurons to take up a large portion of the presynaptic plasma membrane in order to regenerate synaptic vesicle pools. Actin, one of the most abundant proteins in eukaryotic cells, plays an important role in this process, but a detailed mechanistic understanding of the involvement of the cortical actin network is still lacking, in part due to the relatively small size of nerve terminals and the limitation of optical microscopy. We recently discovered that neurosecretory cells display a similar, albeit much larger, form of bulk endocytosis in response to secretagogue stimulation...
May 22, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28545305/clostridium-difficile-toxins-a-and-b-receptors-pores-and-translocation-into-cells
#11
Kathleen E Orrell, Zhifen Zhang, Seiji N Sugiman-Marangos, Roman A Melnyk
The most potent toxins secreted by pathogenic bacteria contain enzymatic moieties that must reach the cytosol of target cells to exert their full toxicity. Toxins such as anthrax, diphtheria, and botulinum toxin all use three well-defined functional domains to intoxicate cells: a receptor-binding moiety that triggers endocytosis into acidified vesicles by binding to a specific host-cell receptor, a translocation domain that forms pores across the endosomal membrane in response to acidic pH, and an enzyme that translocates through these pores to catalytically inactivate an essential host cytosolic substrate...
May 26, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28544880/systems-wide-studies-uncover-commander-a-multiprotein-complex-essential-to-human-development
#12
REVIEW
Anna L Mallam, Edward M Marcotte
Recent mass spectrometry maps of the human interactome independently support the existence of a large multiprotein complex, dubbed "Commander." Broadly conserved across animals and ubiquitously expressed in nearly every human cell type examined thus far, Commander likely plays a fundamental cellular function, akin to other ubiquitous machines involved in expression, proteostasis, and trafficking. Experiments on individual subunits support roles in endosomal protein sorting, including the trafficking of Notch proteins, copper transporters, and lipoprotein receptors...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28542518/rnf41-interacts-with-the-vps52-subunit-of-the-garp-and-earp-complexes
#13
Delphine Masschaele, Leentje De Ceuninck, Joris Wauman, Dieter Defever, Frank Stenner, Sam Lievens, Frank Peelman, Jan Tavernier
RNF41 (Ring Finger Protein 41) is an E3 ubiquitin ligase involved in the intracellular sorting and function of a diverse set of substrates. Next to BRUCE and Parkin, RNF41 can directly ubiquitinate ErbB3, IL-3, EPO and RARα receptors or downstream signaling molecules such as Myd88, TBK1 and USP8. In this way it can regulate receptor signaling and routing. To further elucidate the molecular mechanism behind the role of RNF41 in intracellular transport we performed an Array MAPPIT (Mammalian Protein-Protein Interaction Trap) screen using an extensive set of proteins derived from the human ORFeome collection...
2017: PloS One
https://www.readbyqxmd.com/read/28540373/in-vitro-cellular-behaviors-and-toxicity-assays-of-small-sized-fluorescent-silicon-nanoparticles
#14
Zhaohui Cao, Fei Peng, Zhilin Hu, Binbin Chu, Yiling Zhong, Yuanyuan Su, Sudan He, Yao He
Extensive investigations have been carried out for evaluating the toxicology of various nanomaterials (e.g., carbon- and metal-based nanomaterials), which offer invaluable information for assessing the feasibility of nanomaterial-based wide-ranging applications. In recent years, sufficient efforts have been made to develop fluorescent small-sized silicon nanoparticles (SiNPs) as a novel optical material simultaneously featuring strong fluorescence and ultrahigh photostability, providing high promise for a myriad of biological, biomedical and electronic applications...
May 25, 2017: Nanoscale
https://www.readbyqxmd.com/read/28539410/leishmania-donovani-restricts-mitochondrial-dynamics-to-enhance-mirnp-stability-and-target-rna-repression-in-host-macrophages
#15
Yogaditya Chakrabarty, Suvendra N Bhattacharyya
microRNAs (miRNA), the tiny regulatory RNAs, form complex with Argonaute (Ago) proteins and inhibit gene expression in metazoan cells. While studying parasite invaded macrophages, we have identified a unique mode of gene regulation, where the parasite Leishmania donovani (Ld) causes mitochondrial depolarization, reduces mitochondrial dynamics and restricts turnover of cellular microRNA ribonucleoprotein (miRNP) complexes in infected host cells. This leads to increased stability of miRNPs along with elevated level of Ago2 bound cytokine mRNA in Ld infected macrophages...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539405/tumor-susceptibility-gene-101-tsg101-regulates-predisposition-towards-apoptosis-via-escrt-machinery-accessory-proteins
#16
Zenia Kaul, Oishee Chakrabarti
ESCRT proteins are implicated in myriad cellular processes, including endosome formation, fusion of autophagosomes/amphisomes with lysosomes and apoptosis. The role played by these proteins in either facilitating or protecting against apoptosis is still unclear. In this study, while trying to understand how deficiency of Mahogunin RING Finger 1 (MGRN1) affects cell viability, we uncover a novel role for its interactor, the ESCRT-I protein, TSG101 - it directly participates in mitigating ER stress mediated apoptosis...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28536357/glycosylated-triterpenoids-as-endosomal-escape-enhancers-in-targeted-tumor-therapies
#17
REVIEW
Hendrik Fuchs, Nicole Niesler, Alexandra Trautner, Simko Sama, Gerold Jerz, Hossein Panjideh, Alexander Weng
Protein-based targeted toxins play an increasingly important role in targeted tumor therapies. In spite of their high intrinsic toxicity, their efficacy in animal models is low. A major reason for this is the limited entry of the toxin into the cytosol of the target cell, which is required to mediate the fatal effect. Target receptor bound and internalized toxins are mostly either recycled back to the cell surface or lysosomally degraded. This might explain why no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date although more than 500 targeted toxins have been developed within the last decades...
March 29, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536352/designing-the-sniper-improving-targeted-human-cytolytic-fusion-proteins-for-anti-cancer-therapy-via-molecular-simulation
#18
REVIEW
Anna Bochicchio, Sandra Jordaan, Valeria Losasso, Shivan Chetty, Rodrigo Casasnovas Perera, Emiliano Ippoliti, Stefan Barth, Paolo Carloni
Targeted human cytolytic fusion proteins (hCFPs) are humanized immunotoxins for selective treatment of different diseases including cancer. They are composed of a ligand specifically binding to target cells genetically linked to a human apoptosis-inducing enzyme. hCFPs target cancer cells via an antibody or derivative (scFv) specifically binding to e.g., tumor associated antigens (TAAs). After internalization and translocation of the enzyme from endocytosed endosomes, the human enzymes introduced into the cytosol are efficiently inducing apoptosis...
February 17, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536264/exosomes-from-uninfected-cells-activate-transcription-of-latent-hiv-1
#19
Robert A Barclay, Angela Schwab, Catherine DeMarino, Yao Akpamagbo, Benjamin Lepene, Seble Kassaye, Sergey Iordanskiy, Fatah Kashanchi
HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic infection due to its ability to become latent. We have previously shown a link between HIV-1 infection and exosome production. Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor (TLR) and NF-κB pathways. In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533468/vacuolation-activity-and-intracellular-trafficking-of-artb-the-binding-subunit-of-an-ab5-toxin-produced-by-salmonella-enterica-serovar-typhi
#20
Brock P Herdman, James C Paton, Hui Wang, Travis Beddoe, Adrienne W Paton
Various Salmonella enterica serovars, including S Typhi, encode an AB5 toxin (ArtAB), the A subunit of which is an ADP-ribosyltransferase related to the S1 subunit of pertussis toxin. However, although the A subunit is able to catalyse ADP-ribosylation of host G proteins, a cytotoxic phenotype has yet to be identified for the holotoxin. Here we show that its B subunit pentamer (ArtB) binds to receptors on the surface of Vero (African green monkey kidney), CHO (Chinese hamster ovary), U937 (human monocyte) and HBMEC (human brain microvascular endothelial) cell lines...
May 22, 2017: Infection and Immunity
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