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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/29456132/csf-lamp2-concentrations-are-decreased-in-female-parkinson-s-disease-patients-with-lrrk2-mutations
#3
Andrea C Klaver, Mary P Coffey, Jan O Aasly, David A Loeffler
Lysosome-associated membrane glycoprotein 2 (lamp2) plays critical roles in chaperone-mediated autophagy (CMA) and macroautophagy. Its isoform lamp2a is decreased in Parkinson's disease (PD) substantia nigra. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most known common cause of late-onset PD; although LRRK2 is thought to regulate macroautophagy, the influence of LRRK2 mutations on lamp2 concentrations in the CNS is unknown. To examine this issue we compared lamp2 levels in cerebrospinal fluid (CSF) between sporadic PD (sPD) patients (n = 31), LRRK2 PD patients (n = 20), and healthy control subjects with or without LRRK2 mutations (LRRK2 CTL = 30, CTL = 27)...
March 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29454917/marine-derived-xyloketal-derivatives-exhibit-anti-stress-and-anti-ageing-effects-through-hsf-pathway-in-caenorhabditis-elegans
#4
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
#5
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
#6
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
#7
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
#8
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/29452922/structural-biology-of-the-separase-securin-complex-with-crucial-roles-in-chromosome-segregation
#9
REVIEW
Shukun Luo, Liang Tong
The cysteine protease separase opens the cohesin ring by cleaving its kleisin subunit and is a pivotal cell cycle factor for the transition from metaphase to anaphase. It is inhibited by forming a complex with the chaperone securin, and in vertebrates, also by the Cdk1-cyclin B1 complex. Separase is activated upon the destruction of securin or cyclin B1 by the proteasome, after ubiquitination by the anaphase-promoting complex/cyclosome (APC/C). Here we review recent structures of the active protease segment of Chaetomium thermophilum separase in complex with a substrate-mimic inhibitor and full-length Saccharomyces cerevisiae and Caenorhabditis elegans separase in complex with securin...
February 13, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29452394/treatment-of-hypertrophic-cardiomyopathy-caused-by-cardiospecific-variants-of-fabry-disease-with-chaperone-therapy
#10
Jonas Müntze, Tim Salinger, Daniel Gensler, Christoph Wanner, Peter Nordbeck
No abstract text is available yet for this article.
February 14, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29452364/4-phenylbutyrate-suppresses-the-unfolded-protein-response-without-restoring-protein-folding-in-saccharomyces-cerevisiae
#11
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/29452206/snx10-mediates-alcohol-induced-liver-injury-and-steatosis-via-regulating-chaperone-mediated-autophagy-activation
#12
Yan You, Wan-Zhen Li, Sulin Zhang, Bin Hu, Yue-Xuan Li, Hai-Dong Li, Huan-Huan Tang, Qian-Wen Li, Yun-Yun Guan, Li-Xin Liu, Wei-Lian Bao, Xiaoyan Shen
BACKGROUND & AIMS: Alcoholic liver disease is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlight the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX) 10 has a regulatory function in endo-lysosomal trafficking and stabilization. Here we investigated the roles of SNX10 in CMA activation and the pathogenesis of alcohol-induced liver injury and steatosis...
February 13, 2018: Journal of Hepatology
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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/29445088/cancer-cell-responses-to-hsp70-inhibitor-jg-98-comparison-with-hsp90-inhibitors-and-finding-synergistic-drug-combinations
#20
Julia A Yaglom, Yongmei Wang, Amy Li, Zhenghu Li, Stephano Monti, Ilya Alexandrov, Xiongbin Lu, Michael Y Sherman
Hsp70 is a promising anti-cancer target. Our JG-98 series of Hsp70 inhibitors show anti-cancer activities affecting both cancer cells and tumor-associated macrophages. They disrupt Hsp70 interaction with a co-chaperone Bag3 and affect signaling pathways important for cancer development. Due to a prior report that depletion of Hsp70 causes similar responses as depletion of Hsp90, interest to Hsp70 inhibitors as drug prototypes is hampered by potential similarity of their effects to effects of Hsp90 inhibitors...
February 14, 2018: Scientific Reports
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