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https://www.readbyqxmd.com/read/28319095/rcn1-suppresses-er-stress-induced-apoptosis-via-calcium-homeostasis-and-perk-chop-signaling
#1
S Xu, Y Xu, L Chen, Q Fang, S Song, J Chen, J Teng
Endoplasmic reticulum (ER) stress is caused by the disturbance of ER homeostasis and leads to the activation of the unfolded protein response (UPR), which alleviates stress at an early stage and triggers apoptosis if homeostasis fails over a prolonged timeframe. Here, we report that reticulocalbin 1 (RCN1), a member of the CREC family, is transactivated by nuclear factor kappa B (NF-κB) during ER stress and inhibits ER stress-induced apoptosis. The depletion of RCN1 increases the UPR during drug-induced ER stress by activating PRKR-like ER kinase-CCAAT/enhancer-binding protein-homologous protein (PERK-CHOP) signaling, thus inducing apoptosis...
March 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28315685/abcb10-depletion-reduces-unfolded-protein-response-in-mitochondria
#2
Masato Yano
Mitochondria have many functions, including ATP generation. The electron transport chain (ETC) and the coupled ATP synthase generate ATP by consuming oxygen. Reactive oxygen species (ROS) are also produced by ETC, and ROS damage deoxyribonucleic acids, membrane lipids and proteins. Recent analysis indicate that mitochondrial unfolded protein response (UPR(mt)), which enhances expression of mitochondrial chaperones and proteases to remove damaged proteins, is activated when damaged proteins accumulate in the mitochondria...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28315494/role-of-the-unfolded-protein-response-in-topography-induced-osteogenic-differentiation-in-rat-bone-marrow-mesenchymal-stem-cells
#3
Mengqi Shi, Wen Song, Tianxiao Han, Bei Chang, Guangwen Li, Jianfeng Jin, Yumei Zhang
The topography of biomaterials can significantly influence the osteogenic differentiation of cells. Understanding topographical signal transduction is critical for developing biofunctional surfaces, but the current knowledge is insufficient. Recently, numerous reports have suggested that the unfolded protein response (UPR) and osteogenic differentiation are inter-linked. Therefore, we hypothesize that the UPR pathway may be involved in the topography-induced osteogenesis. In the present study, different surface topographies were fabricated on pure titanium foils and the endoplasmic reticulum (ER) stress and UPR pathway were systematically investigated...
March 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28315173/ricolinostat-a-selective-hdac6-inhibitor-shows-anti-lymphoma-cell-activity-alone-and-in-combination-with-bendamustine
#4
Maria Cosenza, Monica Civallero, Luigi Marcheselli, Stefano Sacchi, Samantha Pozzi
Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry...
March 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28314264/targeting-the-unfolded-protein-response-as-a-potential-therapeutic-strategy-in-renal-carcinoma-cells-exposed-to-cyclosporine-a
#5
Sandra Bodeau, Chloé Sauzay, Rémy Nyga, Christophe Louandre, Véronique Descamps, Catherine François, Corinne Godin, Gabriel Choukroun, Antoine Galmiche
BACKGROUND/AIM: Organ transplant patients treated with the immunosuppressive drug cyclosporine A often present malignant kidney tumors. Cyclosporine A can promote oncogenesis in a cell-intrinsic manner by increasing the production of vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: We explored the impact of cyclosporine A and the role of the unfolded protein response (UPR) on three human renal cell carcinoma (RCC) cell lines under normoxic and hypoxic (1% O2) conditions...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303141/the-function-of-fk506-binding-protein-13-in-protein-quality-control-protects-plasma-cells-from-endoplasmic-reticulum-stress-associated-apoptosis
#6
Mini Jeong, Eunkyeong Jang, Suk San Choi, Changhoon Ji, Kyungho Lee, Jeehee Youn
Plasma cells (PCs) are exposed to intense endoplasmic reticulum (ER) stress imposed by enormous rates of immunoglobulin (Ig) synthesis and secretion. Therefore, protein homeostasis is crucial for the survival of PCs, but its molecular mechanism remains largely unknown. Here, we found marked overexpression of FK506-binding protein 13 (FKBP13) in long-lived PCs from autoimmune mice and investigated its function using a plasmacytoma cell line secreting IgA. FKBP13 expression was induced largely in the lumen of ER in response to treatment with an ER stressor tunicamycin or overexpression of an adaptive unfolded protein response (UPR) protein X-box binding protein 1 (XBP1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28295011/increased-dosage-of-aox1-promoter-regulated-expression-cassettes-leads-to-transcription-attenuation-of-the-methanol-metabolism-in-pichia-pastoris
#7
Elena Cámara, Nils Landes, Joan Albiol, Brigitte Gasser, Diethard Mattanovich, Pau Ferrer
The methanol-regulated alcohol oxidase promoter (PAOX1) of Pichia pastoris is one of the strongest promoters for heterologous gene expression in this methylotrophic yeast. Although increasing gene dosage is one of the most common strategies to increase recombinant protein productivities, the increase of gene dosage of Rhizopus oryzae lipase (ROL) in P. pastoris has been previously shown to reduce cell growth, lipase production and substrate consumption in high-copy strains. To better assess that physiological response, transcriptomics analysis was performed of a subset of strains with 1 to 15 ROL copies...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292956/endoplasmic-reticulum-proteostasis-in-glioblastoma-from-molecular-mechanisms-to-therapeutic-perspectives
#8
REVIEW
Joanna Obacz, Tony Avril, Pierre-Jean Le Reste, Hery Urra, Véronique Quillien, Claudio Hetz, Eric Chevet
Cellular stress induced by the accumulation of misfolded proteins at the endoplasmic reticulum (ER) is a central feature of secretory cells and is observed in many tissues in various diseases, including cancer, diabetes, obesity, and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the cytosol and nucleus to restore proteostasis...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28286750/cellular-pathology-of-pelizaeus-merzbacher-disease-involving-chaperones-associated-with-endoplasmic-reticulum-stress
#9
REVIEW
Ken Inoue
Disease-causing mutations in genes encoding membrane proteins may lead to the production of aberrant polypeptides that accumulate in the endoplasmic reticulum (ER). These mutant proteins have detrimental conformational changes or misfolding events, which result in the triggering of the unfolded protein response (UPR). UPR is a cellular pathway that reduces ER stress by generally inhibiting translation, increasing ER chaperones levels, or inducing cell apoptosis in severe ER stress. This process has been implicated in the cellular pathology of many neurological disorders, including Pelizaeus-Merzbacher disease (PMD)...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28286226/microrna-297-promotes-cardiomyocyte-hypertrophy-via-targeting-sigma-1-receptor
#10
Qinxue Bao, Mingyue Zhao, Li Chen, Yu Wang, Siyuan Wu, Wenchao Wu, Xiaojing Liu
AIMS: Sigma-1 receptor (Sig-1R) is a ligand-regulated endoplasmic reticulum (ER) chaperone involved in cardiac hypertrophy, but it is not known whether Sig-1R is regulated by microRNAs (miRNAs). According to bioinformatic analysis, miR-297 was suggested as a potential target miRNA for Sig-1R. Therefore, we verified whether miR-297 could target Sig-1R and investigated the possible mechanisms underlying the role of miR-297 in cardiac hypertrophy. MAIN METHODS: Bioinformatic analysis combined with laboratory experiments, including quantitative RT-PCR, Western blotting, and luciferase assay, were performed to identify the target miRNA of Sig-1R...
March 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#11
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/28285134/loss-of-gspt1l-disturbs-the-patterning-of-the-brain-central-arteries-in-zebrafish
#12
Hongcheng Wang, Lingfei Luo, Deqin Yang
The cranial vasculature is crucial for the survival and development of the central nervous system and is closely related to brain pathologies. Characterizations of the underlying mechanisms by which cranial vessels acquire their stereotypic patterning remain to be the key interest in the cerebrovascular research. In this report, we show an interesting zebrafish cq37 mutant displaying aberrant patterning of the central arteries. Genetic mapping results indicate that the gene responsible for cq37 encodes G1 to S phase transition 1, like (Gspt1l) with a nonsense mutation...
March 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28279189/therapeutic-strategies-of-drug-repositioning-targeting-autophagy-to-induce-cancer-cell-death-from-pathophysiology-to-treatment
#13
REVIEW
Go J Yoshida
The 2016 Nobel Prize in Physiology or Medicine was awarded to the researcher that discovered autophagy, which is an evolutionally conserved catabolic process which degrades cytoplasmic constituents and organelles in the lysosome. Autophagy plays a crucial role in both normal tissue homeostasis and tumor development and is necessary for cancer cells to adapt efficiently to an unfavorable tumor microenvironment characterized by hypo-nutrient conditions. This protein degradation process leads to amino acid recycling, which provides sufficient amino acid substrates for cellular survival and proliferation...
March 9, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28276702/integrating-the-upr-mt-into-the-mitochondrial-maintenance-network
#14
Christopher J Fiorese, Cole M Haynes
Mitochondrial function is central to many different processes in the cell, from oxidative phosphorylation to the synthesis of iron-sulfur clusters. Therefore, mitochondrial dysfunction underlies a diverse array of diseases, from neurodegenerative diseases to cancer. Stress can be communicated to the cytosol and nucleus from the mitochondria through many different signals, and in response the cell can effect everything from transcriptional to post-transcriptional responses to protect the mitochondrial network...
February 22, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28275095/bap1-inhibits-the-er-stress-gene-regulatory-network-and-modulates-metabolic-stress-response
#15
Fangyan Dai, Hyemin Lee, Yilei Zhang, Li Zhuang, Hui Yao, Yuanxin Xi, Zhen-Dong Xiao, M James You, Wei Li, Xiaoping Su, Boyi Gan
The endoplasmic reticulum (ER) is classically linked to metabolic homeostasis via the activation of unfolded protein response (UPR), which is instructed by multiple transcriptional regulatory cascades. BRCA1 associated protein 1 (BAP1) is a tumor suppressor with de-ubiquitinating enzyme activity and has been implicated in chromatin regulation of gene expression. Here we show that BAP1 inhibits cell death induced by unresolved metabolic stress. This prosurvival role of BAP1 depends on its de-ubiquitinating activity and correlates with its ability to dampen the metabolic stress-induced UPR transcriptional network...
March 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28274921/the-unfolded-protein-response-in-relation-to-mitochondrial-biogenesis-in-skeletal-muscle-cells
#16
Zahra S Mesbah Moosavi, David A Hood
Mitochondria are comprised of both nuclear- and mitochondrially-encoded proteins requiring precise stoichiometry for their integration into functional complexes. The augmented protein synthesis associated with mitochondrial biogenesis results in the accumulation of unfolded proteins, thus triggering cellular stress. As such, the unfolded protein responses emanating from the endoplasmic reticulum (UPR(ER)) or the mitochondrion (UPR(MT)) are triggered to ensure correct protein handling. Whether this response is necessary for mitochondrial adaptations is unknown...
March 8, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28274652/mitochondria-and-epigenetics-crosstalk-in-homeostasis-and-stress
#17
REVIEW
Olli Matilainen, Pedro M Quirós, Johan Auwerx
Through epigenetic mechanisms cells integrate environmental stimuli to fine-tune gene expression levels. Mitochondrial function is essential to provide the intermediate metabolites necessary to generate and modify epigenetic marks in the nucleus, which in turn can regulate the expression of mitochondrial proteins. In this review we summarize the function of mitochondria in the regulation of epigenetic mechanisms as a new aspect of mitonuclear communication. We focus in particular on the most common epigenetic modifications - histone acetylation and histone and DNA methylation...
March 5, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28272317/modulation%C3%A2-of%C3%A2-the%C3%A2-proteostasis%C3%A2-machinery%C3%A2-to%C3%A2-overcome%C3%A2-stress%C3%A2-caused%C3%A2-by%C3%A2-diminished%C3%A2-levels%C3%A2-of%C3%A2-t6a-modified%C3%A2-trnas%C3%A2-in%C3%A2-drosophila
#18
Diego Rojas-Benítez, Cristián Eggers, Alvaro Glavic
Transfer RNAs (tRNAs) harbor a subset of post-transcriptional modifications required for structural stability or decoding function. N6-threonylcarbamoyladenosine (t6A) is a universally conserved modification found at position 37 in tRNA that pair A-starting codons (ANN) and is required for proper translation initiation and to prevent frame shift during elongation. In its absence, the synthesis of aberrant proteins is likely, evidenced by the formation of protein aggregates. In this work, our aim was to study the relationship between t6A-modified tRNAs and protein synthesis homeostasis machinery using Drosophila melanogaster...
March 6, 2017: Biomolecules
https://www.readbyqxmd.com/read/28271591/a-novel-heterozygous-mutation-of-the-wfs1-gene-leading-to-constitutive-endoplasmic-reticulum-stress-is-the-cause-of-wolfram-syndrome
#19
Shuntaro Morikawa, Toshihiro Tajima, Akie Nakamura, Katsura Ishizu, Tadashi Ariga
BACKGROUND: Wolfram syndrome (WS) is a disorder characterized by the association of insulin-dependent diabetes mellitus (DM), diabetes insipidus, deafness, and optic nerve atrophy. WS is caused by WFS1 mutations encoding WFS1 protein expressed in endoplasmic reticulum (ER). During ER protein synthesis, misfolded and unfolded proteins accumulate, known as "ER stress". This is attenuated by the unfolded protein response (UPR), which recovers and maintains ER functions. Because WFS1 is a UPR component, mutant WFS1 might cause unresolvable ER stress conditions and cell apoptosis, the major causes underlying WS symptoms...
March 8, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28271468/the-role-of-endoplasmic-reticulum-stress-in-diabetic-nephropathy
#20
REVIEW
Ying Fan, Kyung Lee, Niansong Wang, John Cijiang He
PURPOSE OF REVIEW: Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a major role in the development and progression of DN. Recent findings suggested that many attributes of DN, such as hyperglycemia, proteinuria, and increased advanced glycation end products and free fatty acids, can all trigger unfolded protein response (UPR) in kidney cells. Herein, we review the current knowledge on the role of ER stress in the setting of kidney injury with a specific emphasis on DN...
March 2017: Current Diabetes Reports
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