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Protein chaperones

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https://www.readbyqxmd.com/read/29457374/proteasomal-function-is-impaired-in-human-osteoarthritic-chondrocytes-and-this-can-contribute-to-decreased-sox9-and-aggrecan
#1
Ramon L Serrano, Liang-Yu Chen, Martin K Lotz, Ru Liu-Bryan, Robert Terkeltaub
OBJECTIVE: Osteoarthritis (OA) chondrocytes have impaired autophagy, one arm of the proteostasis network that coordinates proteome and organelle quality control and degradation. Deficient proteostasis impacts differentiation and viability, and inflammatory processes in aging and disease. Studying OA chondrocytes, we assessed ubiquitin proteasome system proteasomal function. METHODS: We evaluated human knee cartilages by immunohistochemistry, and assessed proteasomal function, levels of proteasomal core subunits and chaperones, and autophagy in cultured chondrocytes...
February 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29456988/effect-of-twine-arginine-translocation-signaling-fusion-system-and-chaperones-co-expression-on-secretory-expression-of-somatropin
#2
Mohammad Reza Bagherinejad, Hamid Mir-Mohammad Sadeghi, Daryoush Abedi, Fateme Moazen, Mohammad Rabbani
Background: Twine-arginine translocation (TAT) system is one of the exporting systems in Escherichia coli which could transport fully/semi-correctly folded proteins outside the reductive cytoplasmic space. In combination with co-expression with a chaperone system, the correctly folded proteins could be transported to oxidative periplasmic space and culture media to pass the main limitations in E. coli expression system such as misfolding and inclusion body formation. Materials and Methods: To study the effectiveness of signaling sequences and chaperone co-expression on the translocation of expressed protein, somatropin was selected as the target...
2018: Advanced Biomedical Research
https://www.readbyqxmd.com/read/29454917/marine-derived-xyloketal-derivatives-exhibit-anti-stress-and-anti-ageing-effects-through-hsf-pathway-in-caenorhabditis-elegans
#3
Jie-Bin Zhou, Ying-Lin Zheng, Yi-Xuan Zeng, Jia-Wei Wang, Zhong Pei, Ji-Yan Pang
Ageing is a complex but universal phenomenon that progressively challenges the homeostasis network and finally leads to the dysfunction of organisms and even death. Previous studies demonstrated that xyloketal B and its derivatives, a series of marine novel ketone compounds, possessed unique antioxidative effects on endothelial and neuronal oxidative injuries. In this study, we examined the effects of xyloketal derivatives on extending lifespan and healthspan of Caenorhabditis elegans. The results showed that most selected xyloketals could protect Caenorhabditis elegans against heat stress and extend the lifespan of worms...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29454675/targeting-immune-driven-opioid-analgesia-by-sigma-1-receptors-opening-the-door-to-novel-perspectives-for-the-analgesic-use-of-sigma-1-antagonists
#4
Miguel Á Tejada, Ángeles Montilla-García, Rafael González-Cano, Inmaculada Bravo-Caparrós, M Carmen Ruiz-Cantero, Francisco R Nieto, Enrique J Cobos
Immune cells have a known role in pronociception, since they release a myriad of inflammatory algogens which interact with neurons to facilitate pain signaling. However, these cells also produce endogenous opioid peptides with analgesic potential. The sigma-1 receptor is a ligand-operated chaperone that modulates neurotransmission by interacting with multiple protein partners, including the μ-opioid receptor. We recently found that sigma-1 antagonists are able to induce opioid analgesia by enhancing the action of endogenous opioid peptides of immune origin during inflammation...
February 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29453988/silencing-calreticulin-gene-might-protect-cardiomyocytes-from-angiotensin-ii-induced-apoptosis
#5
Wen Zhang, Zhiyue Liu, Yanmei Zhang, Qinxue Bao, Wenchao Wu, He Huang, Xiaojing Liu
AIMS: Calreticulin (CRT), as a chaperone, contributes to protein folding and quality control cycle. CRT is an important factor regulating Ca 2+ that participates in cell apoptosis. However, the function of CRT in the heart is still controversial. Therefore, we aimed to investigate the potential role of CRT in angiotensin II-induced cardiomyocytes apoptosis. MAIN METHODS: Primary cultured neonatal cardiomyocytes were stimulated with angiotensin II to induce the apoptosis...
February 14, 2018: Life Sciences
https://www.readbyqxmd.com/read/29453286/chaperone-substrate-provides-missing-link-for-cancer-drug-discovery
#6
Katherine M Byrd, Brian S J Blagg
Both Hsp70 and Hsp90 chaperones are overexpressed in cancer, making them relevant targets for the development of cancer chemotherapeutics, but a lack of biomolecular readouts for Hsp70 inhibition has limited the pursuit of specific inhibitors for this enzyme. A new study from Cesa et al. identifies two inhibitors of apoptosis proteins (IAPs) as specific client substrates of Hsp70. These results establish biomarkers that can be utilized to monitor Hsp70 inhibition and provide a framework for future efforts to deconvolute chaperone networks...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29453283/chemical-stresses-fail-to-mimic-the-unfolded-protein-response-resulting-from-luminal-load-with-unfolded-polypeptides
#7
Timothy J Bergmann, Ilaria Fregno, Fiorenza Fumagalli, Andrea Rinaldi, Francesco Bertoni, Paul J Boersema, Paola Picotti, Maurizio Molinari
The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re-establish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans or redox homeostasis. Cell responses to variations in luminal load with unfolded proteins are, in contrast, poorly characterized...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29452364/4-phenylbutyrate-suppresses-the-unfolded-protein-response-without-restoring-protein-folding-in-saccharomyces-cerevisiae
#8
Chi Thanh Mai, Quynh Giang Le, Yuki Ishiwata-Kimata, Hiroshi Takagi, Kenji Kohno, Yukio Kimata
Accumulation of unfolded secretory proteins in the endoplasmic reticulum (ER), namely ER stress, is hazardous to eukaryotic cells and promotes the unfolded protein response (UPR). Ire1 is an ER-located transmembrane protein that senses ER stress and triggers the UPR. According to previous in vitro experiments, 4-phenylbutyrate (4-PBA) works as a chemical molecular chaperone. Since 4-PBA attenuates the UPR in mammalian tissue cultures, this chemical may have clinical potential for restoring ER-stressing conditions...
February 14, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29450800/the-endogenous-subcellular-localisations-of-the-long-chain-fatty-acid-activating-enzymes-acsl3-and-acsl4-in-sarcoma-and-breast-cancer-cells
#9
Yassmeen Radif, Haarith Ndiaye, Vasiliki Kalantzi, Ruth Jacobs, Andrew Hall, Shane Minogue, Mark G Waugh
Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype...
February 15, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29449316/snareing-an-arp-requires-a-lir
#10
Sharon A Tooze
The fusion of autophagosomes with lysosomes is an obligatory step in the self-eating process of autophagy. In this issue, Kumar et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708039) identify a protein complex, the autophagosome recognition particle (ARP), that chaperones a key SNARE, syntaxin 17, to the autophagosome membrane. Intriguingly, this protein complex coordinates both delivery and membrane insertion as a prelude to fusion.
February 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29449045/how-to-measure-glucocorticoid-receptor-s-sensitivity-in-patients-with-stress-related-psychiatric-disorders
#11
REVIEW
Carolin Leistner, Andreas Menke
Stress is a state of derailed homeostasis and a main environmental risk factor for psychiatric diseases. Chronic or uncontrollable stress may lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is a common feature of stress-related psychiatric disorders. One of the key mechanisms underlying a disturbed HPA axis is an impaired function of the glucocorticoid receptor (GR) with an enhanced or reduced feedback sensitivity for glucocorticoids and subsequently altered concentrations of peripheral cortisol...
February 2, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29448096/ampk-alleviates-endoplasmic-reticulum-stress-by-inducing-the-er-chaperone-orp150-via-foxo1-to-protect-human-bronchial-cells-from-apoptosis
#12
Ji-Qiang Liu, Li Zhang, Ji Yao, Shuo Yao, Ting Yuan
Chronic obstructive pulmonary disease (COPD), is characterized by inflammation of airways accompanied by a progressive destruction of lung parenchyma. This process is initiated in most cases by cigarette smoking. In this study we investigated the role of AMP activated protein kinase (AMPK) in cigarette smoke extract (CSE)-induced airway epithelial cell apoptosis as a consequence of endoplasmic reticulum stress (ER stress). Exposure of human bronchial epithelial cells (HBEpC) to CSE resulted in apoptosis as detected using Annexin V-PI flow cytometry...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29447916/helix-formation-and-stability-in-membranes
#13
REVIEW
Matthew J McKay, Fahmida Afrose, Roger E Koeppe, Denise V Greathouse
In this article we review current understanding of basic principles for the folding of membrane proteins, focusing on the more abundant alpha-helical class. Membrane proteins, vital to many biological functions and implicated in numerous diseases, fold into their active conformations in the complex environment of the cell bilayer membrane. While many membrane proteins rely on the translocon and chaperone proteins to fold correctly, others can achieve their functional form in the absence of any translation apparatus or other aides...
February 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29447283/gp96-deficiency-affects-tlr4-functionality-and-impairs-erk-and-p38-phosphorylation
#14
Jesus Cosin-Roger, Marianne R Spalinger, Pedro A Ruiz, Claudia Stanzel, Anne Terhalle, Lutz Wolfram, Hassan Melhem, Kirstin Atrott, Silvia Lang, Isabelle Frey-Wagner, Michael Fried, Michael Scharl, Martin Hausmann, Gerhard Rogler
Gp96 is an endoplasmic reticulum chaperone for multiple protein substrates. Its lack in intestinal macrophages of Crohn's disease (CD) patients is correlated with loss of tolerance against the host gut flora. Gp96 has been stablished to be an essential chaperone for Toll-like receptors (TLRs). We studied the impact of gp96-knockdown on TLR-function in macrophages. TLR2 and TLR4 expression was only decreased but not abolished when gp96 was knocked-down in cell lines, whereas in a monocyte/macrophage specific knock-out mouse model (LysMCre) TLR4 was abolished, while TLR2 was still present...
2018: PloS One
https://www.readbyqxmd.com/read/29445274/endoplasmic-reticulum-chaperone-grp78-mediates-cigarette-smoke-induced-necroptosis-and-injury-in-bronchial-epithelium
#15
Yong Wang, Jie-Sen Zhou, Xu-Chen Xu, Zhou-Yang Li, Hai-Pin Chen, Song-Min Ying, Wen Li, Hua-Hao Shen, Zhi-Hua Chen
Introduction: Bronchial epithelial cell death and airway inflammation induced by cigarette smoke (CS) have been involved in the pathogenesis of COPD. GRP78, belonging to heat shock protein 70 family, has been implicated in cell death and inflammation, while little is known about its roles in COPD. Here, we demonstrate that GRP78 regulates CS-induced necroptosis and injury in bronchial epithelial cells. Materials and methods: GRP78 and necroptosis markers were examined in human bronchial epithelial (HBE) cell line, primary mouse tracheal epithelial cells, and mouse lungs...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29444822/the-protein-kinase-perk-eif2ak3-regulates-proinsulin-processing-not-via-protein-synthesis-but-by-controlling-endoplasmic-reticulum-chaperones
#16
Carrie R Sowers, Rong Wang, Rebecca A Bourne, Barbara C McGrath, Jingjie Hu, Sarah C Bevilacqua, James C Paton, Adrienne W Paton, Sophie Collardeau-Frachon, Marc Nicolino, Douglas R Cavener
Loss-of-function mutations of the protein kinase PERK (EIF2AK3) in humans and mice cause permanent neonatal diabetes and severe proinsulin aggregation in the endoplasmic reticulum (ER), highlighting the essential role of PERK in insulin production in pancreatic β cells. As PERK is generally known as a translational regulator of the Unfolded Protein Response (UPR), the underlying cause of these β cell defects has often been attributed to derepression of proinsulin synthesis, resulting in proinsulin overload in the ER...
February 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29444815/molecular-mechanisms-of-missense-mutations-that-generate-ectopic-n-glycosylation-sites-in-coagulation-factor-viii
#17
Wei Wei, Saurav Misra, Matthew V Cannon, Renchi Yang, Xiaofan Zhu, Reid Gilmore, Min Zhu, Bin Zhang
N-glycosylation is a common posttranslational modification of secreted and membrane proteins, catalyzed by the two enzymatic isoforms of the oligosaccharyltransferase, STT3A and STT3B. Missense mutations are the most common mutations in inherited diseases, however, missense mutations that generate extra, non-native N-glycosylation sites have not been well characterized. Coagulation factor VIII (FVIII) contains five consensus N-glycosylation sites outside its functionally dispensable B domain. We developed a computer program that identified hemophilia A mutations in FVIII that can potentially create ectopic glycosylation sites...
February 14, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29444814/plastid-translation-elongation-factor-tu-is-prone-to-heat-induced-aggregation-despite-its-critical-role-in-plant-heat-tolerance
#18
Xifeng Li, Chong Cai, Zhe Wang, Baofang Fan, Cheng Zhu, Zhixiang Chen
Translation elongation factor Tu (EF-Tu) is a conserved GTP-binding protein essential for protein translation in prokaryotes and eukaryotic organelles of mitochondria and plastids. EF-Tu also has a GTP/GDP-independent chaperone activity implicated in heat adaptation. Here, we report that Arabidopsis plastid EF-Tu, Rabe1b, rapidly became insoluble in vitro at a temperature as low as 35{degree sign}, but remained largely soluble in vivo at the elevated temperature. At a temperature above 41{degree sign}C, insolubilization of Rabe1b also occurred in vivo, with more than 90% becoming aggregated in 9 hours at 45{degree sign}C...
February 14, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29444421/chloroplast-signaling-gates-thermotolerance-in-arabidopsis
#19
Patrick J Dickinson, Manoj Kumar, Claudia Martinho, Seong Jeon Yoo, Hui Lan, George Artavanis, Varodom Charoensawan, Mark Aurel Schöttler, Ralph Bock, Katja E Jaeger, Philip A Wigge
Temperature is a key environmental variable influencing plant growth and survival. Protection against high temperature stress in eukaryotes is coordinated by heat shock factors (HSFs), transcription factors that activate the expression of protective chaperones such as HEAT SHOCK PROTEIN 70 (HSP70); however, the pathway by which temperature is sensed and integrated with other environmental signals into adaptive responses is not well understood. Plants are exposed to considerable diurnal variation in temperature, and we have found that there is diurnal variation in thermotolerance in Arabidopsis thaliana, with maximal thermotolerance coinciding with higher HSP70 expression during the day...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29443896/dexamethasone-mediated-upregulation-of-calreticulin-inhibits-primary-human-glioblastoma-dispersal-ex-vivo
#20
Mohan Nair, Juan Romero, Aria Mahtabfar, Ahmed M Meleis, Ramsey A Foty, Siobhan A Corbett
Dispersal of Glioblastoma (GBM) renders localized therapy ineffective and is a major cause of recurrence. Previous studies have demonstrated that Dexamethasone (Dex), a drug currently used to treat brain tumor-related edema, can also significantly reduce dispersal of human primary GBM cells from neurospheres. It does so by triggering α5 integrin activity, leading to restoration of fibronectin matrix assembly (FNMA), increased neurosphere cohesion, and reduction of neurosphere dispersal velocity (DV). How Dex specifically activates α5 integrin in these GBM lines is unknown...
February 14, 2018: International Journal of Molecular Sciences
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