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https://www.readbyqxmd.com/read/28331181/multi-walled-carbon-nanotubes-act-as-a-chemokine-and-recruit-macrophages-by-activating-the-plc-ip3-crac-channel-signaling-pathway
#1
Hui Li, Xiao-Qiu Tan, Li Yan, Bo Zeng, Jie Meng, Hai-Yan Xu, Ji-Min Cao
The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322778/down-regulation-of-cyclin-dependent-kinase-4-and-mapk-through-estrogen-receptor-mediated-cell-cycle-arrest-in-human-breast-cancer-induced-by-gold-nanoparticle-tagged-toxin-protein-nkct1
#2
Tanmoy Bhowmik, Antony Gomes
AIM: The aim of this study was to determine whether gold nanoparticles conjugated cytotoxic protein NKCT1 (GNP-NKCT1) acted through the estrogen receptor mediated pathway in MCF-7 cells and to establish the MAPK and PI3k/Akt signal transduction pathway. METHODS: Apoptosis was done by flow cytometry. BrdU incorporation and nuclear proliferating antigen was measured by flow cytometry. Wound healing assay along with matrigel chamber invasion and migration was done...
March 18, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28298446/folding-of-a-single-domain-protein-entering-the-endoplasmic-reticulum-precedes-disulfide-formation
#3
Philip J Robinson, Marie Anne Pringle, Cheryl A Woolhead, Neil J Bulleid
The relationship between protein synthesis, folding and disulfide formation within the endoplasmic reticulum (ER) is poorly understood. Previous studies have suggested pre-existing disulfide links are absolutely required to allow protein folding and, conversely, that protein folding occurs prior to disulfide formation. To address the question of what happens first within the ER; that is, protein folding or disulfide formation, we studied folding events at the early stages of polypeptide chain translocation into the mammalian ER using stalled translation intermediates...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28287444/bufalin-induces-apoptosis-of-human-osteosarcoma-u-2-os-cells-through-endoplasmic-reticulum-stress-caspase-and-mitochondria-dependent-signaling-pathways
#4
Ching-Hsiao Lee, Yung-Luen Shih, Mei-Hui Lee, Man-Kuan Au, Yung-Liang Chen, Hsu-Feng Lu, Jing-Gung Chung
Bone cancer is one of the cancer-related diseases, and there are increased numbers of patients with bone cancer worldwide. Therefore the efficacy of treatment of bone cancer is considered extremely vital. Bufalin has been showed to have biological activities including anticancer activities in vitro and in vivo. However, the exact associated mechanisms for bufalin induced apoptosis in human bone cancer cells are still unclear. In the present study, we investigated the effect of bufalin on the cytotoxic effects in U-2 OS human osteosarcoma cells...
March 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28286511/bhbzip60-from-resurrection-plant-boea-hygrometrica-is-an-mrna-splicing-activated-endoplasmic-reticulum-stress-regulator-involved-in-drought-tolerance
#5
Bo Wang, Hong Du, Zhennan Zhang, Wenzhong Xu, Xin Deng
Adverse environmental conditions cause endoplasmic reticulum (ER) stress in plants. To mitigate ER stress damage, ER associated transcription factors and inositol-requiring enzyme-1 (IRE1)-mediated bZIP60 mRNA splicing are activated in plants. A drought-induced gene, encoding the ortholog of AtbZIP60, was identified in the resurrection plant Boea hygrometrica, termed BhbZIP60. In response to ER stress and dehydration, BhbZIP60 mRNA can be spliced to create a frame shift in the C terminus by the excision of 23b segment in a manner of its ortholog in other plants, thus translocating to the nucleus instead of the cytoplasm...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28286332/two-alternative-binding-mechanisms-connect-the-protein-translocation-sec71-sec72-complex-with-heat-shock-proteins
#6
Arati Tripathi, Elisabet C Mandon, Reid Gilmore, Tom A Rapoport
The biosynthesis of many eukaryotic proteins requires accurate targeting to and translocation across the endoplasmic reticulum (ER) membrane. Post-translational protein translocation in yeast requires both the Sec61 translocation channel, and a complex of four additional proteins: Sec63, Sec62, Sec71, and Sec72. The structure and function of these proteins are largely unknown. This pathway also requires the cytosolic Hsp70 protein Ssa1, but whether Ssa1 associates with the translocation machinery to target protein substrates to the membrane is unclear...
March 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#7
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene (Ensembl ID: ENSG00000044574 (WTSI/EMBL-EBI, 2015)) encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca(2+) homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28284859/molecular-mechanisms-of-3-3-4-4-5-pentachlorobiphenyl-induced-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma-cells
#8
Li Song, Linlin Guo, Zhuoyu Li
Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration...
March 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28261091/ginsenoside-rg5-inhibits-succinate-associated-lipolysis-in-adipose-tissue-and-prevents-muscle-insulin-resistance
#9
Na Xiao, Le-Le Yang, Yi-Lin Yang, Li-Wei Liu, Jia Li, Baolin Liu, Kang Liu, Lian-Wen Qi, Ping Li
Endoplasmic reticulum (ER) stress, inflammation, and lipolysis occur simultaneously in adipose dysfunction and contribute to insulin resistance. This study was designed to investigate whether ginsenoside Rg5 could ameliorate adipose dysfunction and prevent muscle insulin resistance. Short-term high-fat diet (HFD) feeding induced hypoxia with ER stress in adipose tissue, leading to succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activity. Rg5 treatment reduced cellular energy charge, suppressed ER stress and then prevented succinate accumulation in adipose tissue...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28260038/the-nerve-growth-factor-alters-calreticulin-translocation-from-the-endoplasmic-reticulum-to-the-cell-surface-and-its-signaling-pathway-in-epithelial-ovarian-cancer-cells
#10
Carolina Andrea Vera, Lorena Oróstica, Fernando Gabler, Arturo Ferreira, Alberto Selman, Margarita Vega, Carmen Aurora Romero
Ovarian cancer is the seventh most common cancer among women worldwide, causing approximately 120,000 deaths every year. Immunotherapy, designed to boost the body's natural defenses against cancer, appears to be a promising option against ovarian cancer. Calreticulin (CRT) is an endoplasmic reticulum (ER) resident chaperone that, translocated to the cell membrane after ER stress, allows cancer cells to be recognized by the immune system. The nerve growth factor (NGF) is a pro-angiogenic molecule overexpressed in this cancer...
February 28, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28228551/cysteine-residues-in-a-yeast-viral-a-b-toxin-crucially-control-host-cell-killing-via-ph-triggered-disulfide-rearrangements
#11
Yutaka Suzuki, Sara L Schwartz, Nina C Mueller, Manfred J Schmitt
K28 is a viral A/B protein toxin that intoxicates yeast and fungal cells by endocytosis and retrograde transport to the endoplasmic reticulum (ER). While toxin translocation into the cytosol occurs on the oxidized α/β heterodimer, the precise mechanism of how the toxin crosses the ER membrane is unknown. Here we identified pH-triggered toxin-intrinsic thiol rearrangements that crucially control toxin conformation and host cell killing. In the natural habitat and low pH environment of toxin-secreting killer yeasts, K28 is structurally stable and biologically active as disulfide-bonded heterodimer while it forms inactive disulfide-bonded oligomers at neutral pH that are caused by activation and thiol deprotonation of β-subunit cysteines...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28178265/computational-investigation-of-sphingosine-kinase-1-sphk1-and-calcium-dependent-erk1-2-activation-downstream-of-vegfr2-in-endothelial-cells
#12
Hojjat Bazzazi, Aleksander S Popel
Vascular endothelial growth factor (VEGF) is a powerful regulator of neovascularization. VEGF binding to its cognate receptor, VEGFR2, activates a number of signaling pathways including ERK1/2. Activation of ERK1/2 is experimentally shown to involve sphingosine kinase 1 (SphK1) activation and its calcium-dependent translocation downstream of ERK1/2. Here we construct a rule-based computational model of signaling downstream of VEGFR2, by including SphK1 and calcium positive feedback mechanisms, and investigate their consequences on ERK1/2 activation...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28137470/nitroimidazole-derivatives-of-polypyridyl-ruthenium-complexes-towards-understanding-their-anticancer-activity-and-mode-of-action
#13
Olga Mazuryk, Oksana Krysiak-Foria, Agnieszka Żak, Franck Suzenet, Agata Ptak-Belowska, Tomasz Brzozowski, Grażyna Stochel, Małgorzata Brindell
The mechanism of cell death induced by the ruthenium polypyridyl complexes comprising two 4,7-diphenyl-1,10-phenanthroline ligands as well as one unmodified 2,2'-bipyridyl or modified with 2-nitroimidazole moiety attached by shorter (C3H6) or longer (C6H12) linker was investigated. Cytotoxicity and proliferation assays revealed that the studied Ru polypyridyl complexes are more toxic against human pancreas carcinoma PANC-1 cell line than normal human keratinocytes HaCaT with IC50 of 3-5μM. The Ru complexes despite accumulation in mitochondria do not lead to mitochondrial disfunction, though decreasing of mitochondrial Ca(2+) causes mitochondria membrane hyperpolarization...
April 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28132902/membrane-insertion-and-topology-of-the-translocon-associated-protein-trap-gamma-subunit
#14
Manuel Bañó-Polo, Carlos A Martínez-Garay, Brayan Grau, Luis Martínez-Gil, Ismael Mingarro
Translocon-associated protein (TRAP) complex is intimately associated with the ER translocon for the insertion or translocation of newly synthesised proteins in eukaryotic cells. The TRAP complex is comprised of three single-spanning and one multiple-spanning subunits. We have investigated the membrane insertion and topology of the multiple-spanning TRAP-γ subunit by glycosylation mapping and green fluorescent protein fusions both in vitro and in cell cultures. Results demonstrate that TRAP-γ has four transmembrane (TM) segments, an Nt/Ct cytosolic orientation and that the less hydrophobic TM segment inserts efficiently into the membrane only in the cellular context of full-length protein...
January 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28132838/human-cytomegalovirus-tegument-protein-ul82-inhibits-sting-mediated-signaling-to-evade-antiviral-immunity
#15
Yu-Zhi Fu, Shan Su, Yi-Qun Gao, Pei-Pei Wang, Zhe-Fu Huang, Ming-Ming Hu, Wei-Wei Luo, Shu Li, Min-Hua Luo, Yan-Yi Wang, Hong-Bing Shu
Recognition of human cytomegalovirus (HCMV) DNA by the cytosolic sensor cGAS initiates STING-dependent innate antiviral responses. HCMV can antagonize host immune responses to promote latency infection. However, it is unknown whether and how HCMV targets the cGAS-STING axis for immune evasion. Here we identified the HCMV tegument protein UL82 as a negative regulator of STING-dependent antiviral responses. UL82 interacted with STING and impaired STING-mediated signaling via two mechanisms. UL82 inhibited the translocation of STING from the ER to perinuclear microsomes by disrupting the STING-iRhom2-TRAPβ translocation complex...
February 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28098884/renin-angiotensin-system-activation-accelerates-atherosclerosis-in-experimental-renal-failure-by-promoting-endoplasmic-reticulum-stress-related-inflammation
#16
Jia Yang, Xi Zhang, Xinyi Yu, Weixue Tang, Hua Gan
In this study, we investigated the association between the renin-angiotensin system (RAS), endoplasmic reticulum (ER) stress and atherosclerosis (AS) in uremic apolipoprotein E knockout (apoE-/-) mice. Mild uremia was induced by a 5/6 nephrectomy (5/6 Nx) in 10-week-old apoE-/- mice. Four weeks after nephrectomy, the mice received losartan or no treatment for 16 weeks. Sham-operated mice served as the controls. We found that uremia accelerated AS at the aortic root. The activation of ER stress and the significant upregulation of pro-inflammatory cytokines and chemokines were observed in the uremic mice...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28089882/a-highly-efficient-modified-human-serum-albumin-signal-peptide-to-secrete-proteins-in-cells-derived-from-different-mammalian-species
#17
Carolina Attallah, Marina Etcheverrigaray, Ricardo Kratje, Marcos Oggero
Signal peptides (SPs) are key elements in the production of recombinant proteins; however, little information is available concerning different SP in mammalian cells other than CHO. In order to study the efficiency of different SPs to direct the traffic along the secretory pathway of the green fluorescence protein (GFP) and a scFv-Fc fusion protein; CHO-K1, HEK293 and NS0 cell lines were transfected in a transient and stable way. SP of human azurocidin (AZ), modified human albumin (mSA), modified Cricetulus griseus Ig kappa chain V III region MOPC 63 like (mIgκ C) and modified human Ig kappa chain V III region VG (mIgκ H) were evaluated...
January 10, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28088515/the-membrane-tethered-nac-transcription-factor-atntl7-contributes-to-er-stress-resistance-in-arabidopsis
#18
Yong Hun Chi, Sarah Mae Boyles Melencion, Cresilda Vergara Alinapon, Min Ji Kim, Eun Seon Lee, Seol Ki Paeng, Joung Hun Park, Ganesh M Nawkar, Young Jun Jung, Ho Byeong Chae, Chang Ho Kang, Sang Yeol Lee
We screened for endoplasmic reticulum (ER) stress-resistant mutants among 25 mutants of the Arabidopsis NTL (NAC with Transmembrane motif 1-Like) family. We identified a novel mutant, SALK_044777, showing strong resistance to ER stress. RT-PCR and genomic DNA sequence analyses identified the mutant as atntl7, which harbors a T-DNA insertion in the fourth exon of AtNTL7. Two other atntl7-mutant alleles, in which T-DNA was inserted in the second exon and third intron of AtNTL7, respectively, showed ER-stress sensitive phenotypes, suggesting that SALK_044777 is a gain-of-function mutant...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28062198/plasma-from-pre-pubertal-obese-children-impairs-insulin-stimulated-nitric-oxide-no-bioavailability-in-endothelial-cells-role-of-er-stress
#19
Natalia Di Pietro, M Loredana Marcovecchio, Sara Di Silvestre, Tommaso de Giorgis, Vincenzo Giuseppe Pio Cordone, Paola Lanuti, Francesco Chiarelli, Giuseppina Bologna, Angelika Mohn, Assunta Pandolfi
Childhood obesity is commonly associated with early signs of endothelial dysfunction, characterized by impairment of insulin signaling and vascular Nitric Oxide (NO) availability. However, the underlying mechanisms remain to be established. Hence, we tested the hypothesis that endothelial insulin-stimulated NO production and availability was impaired and related to Endoplasmic Reticulum (ER) in human umbilical vein endothelial cells (HUVECs) cultured with plasma obtained from pre-pubertal obese (OB) children...
March 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28057769/extra-nuclear-effects-of-estrogen-on-cortical-bone-in-males-require-er%C3%AE-af-1
#20
H H Farman, J Wu, K L Gustafsson, S H Windahl, S H Kim, J A Katzenellenbogen, C Ohlsson, M K Lagerquist
Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects...
February 2017: Journal of Molecular Endocrinology
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