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https://www.readbyqxmd.com/read/28815021/toward-an-understanding-of-the-cdc48-p97-atpase
#1
REVIEW
Nicholas Bodnar, Tom Rapoport
A conserved AAA+ ATPase, called Cdc48 in yeast and p97 or VCP in metazoans, plays an essential role in many cellular processes by segregating polyubiquitinated proteins from complexes or membranes. For example, in endoplasmic reticulum (ER)-associated protein degradation (ERAD), Cdc48/p97 pulls polyubiquitinated, misfolded proteins out of the ER and transfers them to the proteasome. Cdc48/p97 consists of an N-terminal domain and two ATPase domains (D1 and D2). Six Cdc48 monomers form a double-ring structure surrounding a central pore...
2017: F1000Research
https://www.readbyqxmd.com/read/28782633/plasma-cell-deficiency-in-humans-with-heterozygous-mutations-in-sec61a1
#2
Desirée Schubert, Marie-Christine Klein, Sarah Hassdenteufel, Andrés Caballero-Oteyza, Linlin Yang, Michele Proietti, Alla Bulashevska, Janine Kemming, Johannes Kühn, Sandra Winzer, Stephan Rusch, Manfred Fliegauf, Alejandro A Schäffer, Stefan Pfeffer, Roger Geiger, Adolfo Cavalié, Hongzhi Cao, Fang Yang, Yong Li, Marta Rizzi, Hermann Eibel, Robin Kobbe, Amy L Marks, Brian P Peppers, Robert W Hostoffer, Jennifer M Puck, Richard Zimmermann, Bodo Grimbacher
BACKGROUND: Primary antibody deficiencies (PAD) are the most frequent primary immunodeficiencies in humans. The genetic causes for PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum (ER) membrane. SEC61A1 is a target gene of XBP1s and strongly induced during plasma cell differentiation. OBJECTIVE: Characterization of a novel genetic defect and its pathological mechanism in eleven patients from two unrelated families with PAD...
August 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28764904/photosensitized-methyl-paraben-induces-apoptosis-via-caspase-dependent-pathway-under-ambient-uvb-exposure-in-human-skin-cells
#3
Divya Dubey, Deepti Chopra, Jyoti Singh, Ajeet K Srivastav, Smita Kumari, Ankit Verma, Ratan Singh Ray
Methyl paraben (MP), is a widely used preservative in pharmaceutical, food and cosmetic products. Its molecular mechanism under ambient ultraviolet radiation is not well understood. We investigated photosensitizing mechanism of MP under ambient UVB (0.6 mW/cm(2)) intensity. MP showed dose dependent decrease in cell viability of human keratinocyte cell line (HaCaT) by MTT and NRU assays. Study showed 40% reduction in antimicrobial activity of UVB irradiated MP through E. coli culture. Photosensitized MP (25 μg/ml) significantly enhanced lipid peroxidation, intracellular ROS generation and disrupted mitochondrial membrane integrity...
July 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28743992/endotoxemia-mediated-activation-of-acetyltransferase-p300-impairs-insulin-signaling-in-obesity
#4
Jia Cao, Jinghua Peng, Hongying An, Qiyi He, Tatiana Boronina, Shaodong Guo, Morris F White, Philip A Cole, Ling He
Diabetes and obesity are characterized by insulin resistance and chronic low-grade inflammation. An elevated plasma concentration of lipopolysaccharide (LPS) caused by increased intestinal permeability during diet-induced obesity promotes insulin resistance in mice. Here, we show that LPS induces endoplasmic reticulum (ER) stress and protein levels of P300, an acetyltransferase involved in glucose production. In high-fat diet fed and genetically obese ob/ob mice, P300 translocates from the nucleus into the cytoplasm of hepatocytes...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28740693/disease-flare-after-discontinuing-gefitinib-in-a-patient-with-lung-adenocarcinoma-and-concomitant-epithelial-growth-factor-receptor-mutation-and-anaplastic-lymphoma-kinase-translocation
#5
Eun Hye Park, Hwa Young Lee, Jin Woo Kim, Chang Dong Yeo
We report on a patient with lung adenocarcinoma and a concomitant epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation who developed a disease flare after discontinuing gefitinib. A 63-year-old woman with lung adenocarcinoma and a concomitant activating EGFR mutation and ALK translocation was treated with first-line gefitinib. After 4 months, she discontinued the gefitinib due to disease progression. She was admitted to the emergency room complaining of severe dyspnea and back pain 22 days after discontinuing gefitinib...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28740138/alantolactone-induces-apoptosis-promotes-stat3-glutathionylation-and-enhances-chemosensitivity-of-a549-lung-adenocarcinoma-cells-to-doxorubicin-via-oxidative-stress
#6
Amara Maryam, Tahir Mehmood, He Zhang, Yongming Li, Muhammad Khan, Tonghui Ma
Alantolactone (ALT), a sesquiterpene lactone component of Inula helenium, has been reported to exert anticancer activity in various cancers. However, the cellular targets and underlying mechanism of anticancer activity of ALT in various cancers including lung cancer has not been fully defined. In the present study, we found that ALT effectively inhibits proliferation and triggers oxidative stress mediated-apoptosis in A549 lung adenocarcinoma cells by inducing ER stress and mitochondrial dysfunction. This ALT-mediated apoptosis was inhibited by NAC while diamide potentiated it...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28711624/curcumin-attenuates-oxidative-stress-induced-nf%C3%AE%C2%BAb-mediated-inflammation-and-endoplasmic-reticulum-dependent-apoptosis-of-splenocytes-in-diabetes
#7
Kahkashan Rashid, Sayantani Chowdhury, Sumit Ghosh, Parames C Sil
The present study was aimed to determine the curative role of curcumin against diabetes induced oxidative stress and its associated splenic complications. Diabetes was induced in the experimental rats via the intraperitoneal administration of a single dose of STZ (65 mg kg(-1) body weight). Increased blood glucose and intracellular ROS levels along with decreased body weight, the activity of cellular antioxidant enzymes and GSH/GSSG ratio were observed in the diabetic animals. Histological assessment showed white pulp depletion and damaged spleen anatomy in these animals...
July 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28706146/ros-independent-nrf2-activation-in-prostate-cancer
#8
Ilaria Bellezza, Paolo Scarpelli, Salvatore V Pizzo, Silvia Grottelli, Egidia Costanzi, Alba Minelli
In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the endoplasmic reticulum that, when expressed at the cell surface, acts as a receptor for several signaling pathways enhancing antiapoptotic and proliferative signals...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700330/translocation-of-heme-oxygenase-1-contributes-to-imatinib-resistance-in-chronic-myelogenous-leukemia
#9
Bianca Schaefer, Soenke Behrends
Heme oxygenase-1 (HO-1) degrades heme to bilirubin. In addition, it is upregulated in malignant disease and has been described as an important factor for cancer prognosis and therapy. Under physiological conditions HO-1 is anchored to the endoplasmic reticulum (ER). Under stress conditions HO-1 can be cleaved and subsequently translocates to the cytosol and nucleus.In this study we systematically investigated the influence of HO-1's catabolic activity and subcellular localization on resistance against the tyrosine kinase inhibitor imatinib in leukemia cells by confocal laser scanning microscopy, hemoglobin synthesis experiments and cell viability assays...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696297/mtorc1-activates-srebp-2-by-suppressing-cholesterol-trafficking-to-lysosomes-in-mammalian-cells
#10
Walaa Eid, Kristin Dauner, Kevin C Courtney, AnneMarie Gagnon, Robin J Parks, Alexander Sorisky, Xiaohui Zha
mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing cholesterol delivery to the ER...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28696214/epigenetic-regulation-by-agonist-specific-aryl-hydrocarbon-receptor-recruitment-of-metastasis-associated-protein-2-selectively-induces-stanniocalcin-2-expression
#11
Aditya D Joshi, Ekram Hossain, Cornelis J Elferink
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a plethora of target genes. Historically, the AhR has been studied as a regulator of xenobiotic metabolizing enzyme genes, notably cytochrome P4501A1 encoded by CYP1A1, in response to the exogenous prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR activity depends on its binding to the xenobiotic response element (XRE) in partnership with the AhR nuclear translocator (Arnt). Recent studies identified stanniocalcin 2 (Stc2) as a novel AhR target gene responsive to the endogenous AhR agonist cinnabarinic acid (CA)...
September 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28682307/cryo-em-structure-of-the-protein-conducting-erad-channel-hrd1-in-complex-with-hrd3
#12
Stefan Schoebel, Wei Mi, Alexander Stein, Sergey Ovchinnikov, Ryan Pavlovicz, Frank DiMaio, David Baker, Melissa G Chambers, Huayou Su, Dongsheng Li, Tom A Rapoport, Maofu Liao
Misfolded endoplasmic reticulum (ER) proteins are retro-translocated through the membrane into the cytosol, where they are poly-ubiquitinated, extracted from the ER membrane, and degraded by the proteasome(1-4), a pathway termed ER-associated protein degradation (ERAD). Proteins with misfolded domains in the ER lumen or membrane are discarded through the ERAD-L and -M pathways, respectively. In S. cerevisiae, both pathways require the ubiquitin ligase Hrd1, a multi-spanning membrane protein with a cytosolic RING finger domain(5,6)...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/28679634/sec61-blockade-by-mycolactone-inhibits-antigen-cross-presentation-independently-of-endosome-to-cytosol-export
#13
Jeff E Grotzke, Patrycja Kozik, Jean-David Morel, Francis Impens, Natalia Pietrosemoli, Peter Cresswell, Sebastian Amigorena, Caroline Demangel
Although antigen cross-presentation in dendritic cells (DCs) is critical to the initiation of most cytotoxic immune responses, the intracellular mechanisms and traffic pathways involved are still unclear. One of the most critical steps in this process, the export of internalized antigen to the cytosol, has been suggested to be mediated by Sec61. Sec61 is the channel that translocates signal peptide-bearing nascent polypeptides into the endoplasmic reticulum (ER), and it was also proposed to mediate protein retrotranslocation during ER-associated degradation (a process called ERAD)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28670397/combined-administration-of-a-sedative-dose-sevoflurane-and-60-oxygen-reduces-inflammatory-responses-to-sepsis-in-animals-and-in-human-pmbcs
#14
Er-Fei Zhang, Zuo-Xu Hou, Tian Shao, Wan-Wan Yang, Bin Hu, Xiao-Xia Wang, Ze-Xin Zhang, Yi Huang, Li-Ze Xiong, Li-Chao Hou
Our study aims to investigate the effects of the inhalation of subanesthestic doses of sevoflurane combined with oxygen on sepsis. Male Sprague-Dawley rats or Male ICR/Km mice underwent caecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysccharide (LPS) to induce sepsis, while sham rats were used as control. Then, rats were treated with the inhalation of sevoflurane in oxygen; and air or 100% oxygen was used as control. Seven-day survival, lung injury and inflammatory factors were assessed...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28670265/the-endoplasmic-reticulum-unfolded-protein-response-in-neurodegenerative-disorders-and-its-potential-therapeutic-significance
#15
REVIEW
Paolo Remondelli, Maurizio Renna
In eukaryotic cells, the endoplasmic reticulum (ER) is the cell compartment involved in secretory protein translocation and quality control of secretory protein folding. Different conditions can alter ER function, resulting in the accumulation of unfolded or misfolded proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated adaptive response known as the unfolded protein response (UPR) that aims to restore proteostasis within the secretory pathway. Conversely, in prolonged cell stress or insufficient adaptive response, UPR signaling causes cell death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28657720/disassembly-of-dipeptide-single-crystals-can-transform-the-lipid-membrane-into-a-network
#16
Meifang Fu, Qi Li, Bingbing Sun, Yang Yang, Luru Dai, Tommy Nylander, Junbai Li
Coupling between cytoskeleton and membranes is critical to cell movement as well as organelle formation. Here, we demonstrate that self-assembled single crystals of a dipeptide, diphenylalanine (FF), can interact with liposomes to form cytoskeleton-like structures. Under a physiological condition, disassembly of FF crystals deforms and translocates supported lipid membrane. The system exhibits similar dynamic characteristics to the endoplasmic reticulum (ER) network in cells. This bottom-up system thus indicates that external matter can participate in the deformation of liposomes, and disassembly of the nanostructures enables a system with distinct dynamic behaviors...
July 25, 2017: ACS Nano
https://www.readbyqxmd.com/read/28640879/dual-targeting-of-a-virus-movement-protein-to-er-and-plasma-membrane-subdomains-is-essential-for-plasmodesmata-localization
#17
Kazuya Ishikawa, Masayoshi Hashimoto, Akira Yusa, Hiroaki Koinuma, Yugo Kitazawa, Osamu Netsu, Yasuyuki Yamaji, Shigetou Namba
Plant virus movement proteins (MPs) localize to plasmodesmata (PD) to facilitate virus cell-to-cell movement. Numerous studies have suggested that MPs use a pathway either through the ER or through the plasma membrane (PM). Furthermore, recent studies reported that ER-PM contact sites and PM microdomains, which are subdomains found in the ER and PM, are involved in virus cell-to-cell movement. However, functional relationship of these subdomains in MP traffic to PD has not been described previously. We demonstrate here the intracellular trafficking of fig mosaic virus MP (MPFMV) using live cell imaging, focusing on its ER-directing signal peptide (SPFMV)...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28636360/proneurogenic-effects-of-trazodone-in-murine-and-human-neural-progenitor-cells
#18
Valeria Bortolotto, Francesca Mancini, Giorgina Mangano, Rita Salem, Er Xia, Erika Del Grosso, Michele Bianchi, Pier Luigi Canonico, Lorenzo Polenzani, Mariagrazia Grilli
Several antidepressants increase adult hippocampal neurogenesis (ahNG) in rodents, primates, and, potentially, humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opportunity for increasing our knowledge on their distinctive peculiarities and for dissecting the contribution of receptor subtypes in ahNG modulation. The aim of this study was to evaluate, in vitro, the effects of the antidepressant trazodone (TZD) on ahNG by using primary cultures of murine adult hippocampal neural progenitor cells (ahNPCs) and human induced pluripotent stem cell (iPSC)-derived NPCs...
July 3, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28624455/cellular-localization-of-atbf1-protein-and-its-functional-implication-in-breast-epithelial-cells
#19
Mei Li, Chi Zhang, Yi Zhong, Jiyuan Zhao
ATBF1, a large transcription factor, was normally localized in nuclei, and its mislocalization to cytoplasm was reported in multiple cancers. However, localization of ATBF1 in breast epithelial cells and its potential functions were unknown. Here, we investigated ATBF1 localization via immunofluorescence staining in different kinds of breast epithelial cells. In MCF10A cells and normal mice mammary gland tissues, ATBF1 was mainly localized in nuclei. Knockdown of ATBF1 expression in MCF10A cells by siRNA promoted cell proliferation...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28624220/tat-hafgf14-154-upregulates-adam10-to-attenuate-the-alzheimer-phenotype-of-app-ps1-mice-through-the-pi3k-creb-ire1%C3%AE-xbp1-pathway
#20
Tian Meng, Qin Cao, Peng Lei, Ashley I Bush, Qi Xiang, Zhijian Su, Xiang He, Jack T Rogers, Ing-Ming Chiu, Qihao Zhang, Yadong Huang
Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer's disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14-154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14-154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in the brain...
June 16, 2017: Molecular Therapy. Nucleic Acids
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