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https://www.readbyqxmd.com/read/29474750/suppressed-heat-shock-protein-response-in-the-kidney-of-exercise-trained-diabetic-rats
#1
J Lappalainen, N K J Oksala, D E Laaksonen, S Khanna, T Kokkola, K Kaarniranta, C K Sen, M Atalay
Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. The present study evaluated the effects of 8-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes...
February 23, 2018: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/29471895/etv6-flt3-fusion-is-a-novel-client-protein-of-hsp90
#2
Bui Thi Kim Ly, Hoang Thanh Chi
FMS-like tyrosine kinase-3 fragments from exon 14 to the end without any mutations or deletions has been reported to fuse to ETV6 (TEL) in a few cases of myeloid/lymphoid neoplasms with eosinophilia carrying a translocation t(12;13)(p13;q12). This fusion protein confers constitutive activation on FLT3 fragment and induces factor-independent growth in transfected Ba/F3 cells indicating that it is an oncoprotein. However, the mechanism controlling the stability of this oncoprotein is unknown. In this study, we focus on finding factors controlling the stability of ETV6/FLT3...
February 22, 2018: Oncology Research
https://www.readbyqxmd.com/read/29471019/hsp90-co-chaperone-p23-contributes-to-dopaminergic-mitochondrial-stress-via-stabilization-of-phd2-implications-for-parkinson-s-disease
#3
Anand Rane, Subramanian Rajagopalan, Manuj Ahuja, Bobby Thomas, Shankar J Chinta, Julie K Andersen
The heat shock factor 90 (hsp90) complex has long been associated with neuropathological phenotypes linked to Parkinson's disease (PD) and its inhibition is neuroprotective in disease models. Hsp90 is conventionally believed to act by suppressing induction of hsp70. Here, we report a novel hsp70-independent mechanism by which Hsp90 may also contribute to PD-associated neuropathology. We previously reported that inhibition of the enzyme prolyl hydroxylase domain 2 (PHD2) in conjunction with increases in hypoxia-inducible factor 1 alpha (HIF1α) results in protection of vulnerable dopaminergic substantia nigra pars compacta (DAergic SNpc) neurons in in vitro and in vivo models of PD...
February 19, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29470645/branching-the-tel2-pathway-for-exact-fit-on-phosphatidylinositol-3-kinase-related-kinases
#4
REVIEW
Katsunori Sugimoto
Phosphatidylinositol 3-kinase-related kinases (PIKKs), are structurally related to phosphatidylinositol 3-kinase (lipid kinase), but possess protein kinase activities. PIKKs include ATM, ATR, DNA-PK, mTOR and SMG1, key regulators of cell proliferation and genome maintenance. TRRAP, which is devoid of protein kinase activity, is the sixth member of the PIKK family. PIKK family members are gigantic proteins in the range of 300-500 kDa. It has become apparent in the last decade that the stability or maturation of the PIKK family members depends on a molecular chaperone called the Tel2-Tti1-Tti2 (TTT) complex...
February 22, 2018: Current Genetics
https://www.readbyqxmd.com/read/29463764/functional-and-physical-interaction-between-yeast-hsp90-and-hsp70
#5
Andrea N Kravats, Joel R Hoskins, Michael Reidy, Jill L Johnson, Shannon M Doyle, Olivier Genest, Daniel C Masison, Sue Wickner
Heat shock protein 90 (Hsp90) is a highly conserved ATP-dependent molecular chaperone that is essential in eukaryotes. It is required for the activation and stabilization of more than 200 client proteins, including many kinases and steroid hormone receptors involved in cell-signaling pathways. Hsp90 chaperone activity requires collaboration with a subset of the many Hsp90 cochaperones, including the Hsp70 chaperone. In higher eukaryotes, the collaboration between Hsp90 and Hsp70 is indirect and involves Hop, a cochaperone that interacts with both Hsp90 and Hsp70...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29462340/expression-patterns-of-srb1-and-other-stress-related-genes-in-candida-albicans-under-oxidative-hyperosmotic-and-thermal-stress
#6
Laiqiang Gao, Haiying Wang, Xuehong Wang, Ailan Li, Qiang Ma
Candida albicans, a human fungal pathogen, is able to tolerate certain levels of environmental stresses. Its cell wall plays an important role in cellular homeostasis, responding to environmental stimuli. SRB1 gene encodes a GDP-mannose pyrophosphorylase that catalyzes the formation of the major cell wall component, mannan. The exact relationship between SRB1 and various stresses is not yet fully understood. In current study, C. albicans SC5314 cells were exposed to oxidative, hyperosmotic, and thermal stresses...
February 14, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
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/29449045/how-to-measure-glucocorticoid-receptor-s-sensitivity-in-patients-with-stress-related-psychiatric-disorders
#8
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/29445088/cancer-cell-responses-to-hsp70-inhibitor-jg-98-comparison-with-hsp90-inhibitors-and-finding-synergistic-drug-combinations
#9
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
https://www.readbyqxmd.com/read/29443086/using-three-color-single-molecule-fret-to-study-the-correlation-of-protein-interactions
#10
Markus Götz, Philipp Wortmann, Sonja Schmid, Thorsten Hugel
Single-molecule Förster resonance energy transfer (smFRET) has become a widely used biophysical technique to study the dynamics of biomolecules. For many molecular machines in a cell proteins have to act together with interaction partners in a functional cycle to fulfill their task. The extension of two-color to multi-color smFRET makes it possible to simultaneously probe more than one interaction or conformational change. This not only adds a new dimension to smFRET experiments but it also offers the unique possibility to directly study the sequence of events and to detect correlated interactions when using an immobilized sample and a total internal reflection fluorescence microscope (TIRFM)...
January 30, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29438624/lessons-from-cancer-subcellular-drug-targeting-of-mitochondrial-hsp90-in-pulmonary-arterial-hypertension
#11
Wolfgang M Kuebler
No abstract text is available yet for this article.
February 13, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29438315/synthesis-and-evaluation-of-the-tumor-cell-growth-inhibitory-potential-of-new-putative-hsp90-inhibitors
#12
Ana Bizarro, Diana Sousa, Raquel T Lima, Loana Musso, Raffaella Cincinelli, Vantina Zuco, Michelandrea De Cesare, Sabrina Dallavalle, M Helena Vasconcelos
BACKGROUND: Heat shock protein 90 (HSP90) is a well-known target for cancer therapy. In a previous work, some of us have reported a series of 3-aryl-naphtho[2,3- d ]isoxazole-4,9-diones as inhibitors of HSP90. METHODS: In the present work, various compounds with new chromenopyridinone and thiochromenopyridinone scaffolds were synthesized as potential HSP90 inhibitors. Their binding affinity to HSP90 was studied in vitro. Selected compounds ( 5 and 8 ) were further studied in various tumor cell lines regarding their potential to cause cell growth inhibition, alter the cell cycle profile, inhibit proliferation, and induce apoptosis...
February 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29437790/her3-mediated-resistance-to-hsp90-inhibition-detected-in-breast-cancer-xenografts-by-affibody-based-pet-imaging
#13
Carlos Daniel Martins, Chiara Da Pieve, Thomas A Burley, Rhodri Smith, Daniela M Ciobota, Louis Allott, Kevin Harrington, Wim J G Oyen, Graham Smith, Gabriela Kramer-Marek
PURPOSE: Recent studies have highlighted a role of human epidermal growth factor receptor 3 (HER3) in HER2-driven cancers (e.g. breast cancer) implicating the up-regulation of the receptor in resistance to HER-targeted therapies and Hsp90 inhibitors (e.g. AUY922). Therefore, we have developed an affibody-based PET radioconjugate that quantitatively assesses HER3 changes induced by Hsp90 inhibition in vivo Experimental Design: Z HER3:8698 affibody molecules were conjugated via the C-terminus cysteine to DFO-maleimide for 89 Zr radiolabeling...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436674/the-targeted-inhibition-of-hsp90-by-a-synthetic-small-molecule-dpide-offers-an-effective-treatment-strategy-against-tnbcs
#14
Yong Jin Oh, Sun You Park, Young Ho Seo
Triple-negative breast cancers (TNBCs) are the most aggressive and metastatic subtype of breast cancers and exhibit poor clinical outcome due to the lack of drug target receptors such as estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (Her2). The limited effectiveness of therapeutic options and the poor prognosis of TNBC patients emphasize the urgent need for identifying new therapeutic agents. In this regard, heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of TNBCs...
February 7, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29434648/hsp90%C3%AE-knockdown-in-dio-mice-reverses-insulin-resistance-and-improves-glucose-tolerance
#15
Enxuan Jing, Pragalath Sundararajan, Ishita Deb Majumdar, Suwagmani Hazarika, Samantha Fowler, Angela Szeto, Stephane Gesta, Armando J Mendez, Vivek K Vishnudas, Rangaprasad Sarangarajan, Niven R Narain
Background: Inhibition of Hsp90 has been shown to improve glucose tolerance and insulin sensitivity in mouse models of diabetes. In the present report, the specific isoform Hsp90ab1, was identified as playing a major role in regulating insulin signaling and glucose metabolism. Methods: In a diet-induced obese (DIO) mouse model of diabetes, expression of various Hsp90 isoforms in skeletal tissue was examined. Subsequent experiments characterized the role of Hsp90ab1 isoform in glucose metabolism and insulin signaling in primary human skeletal muscle myoblasts (HSMM) and a DIO mouse model...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29434293/luminescence-resonance-energy-transfer-between-genetically-encoded-donor-and-acceptor-for-protein-protein-interaction-studies-in-the-molecular-chaperone-hsp70-hsp90-complexes
#16
Kaushik Bhattacharya, Lilia Bernasconi, Didier Picard
Complex patterns of protein-protein interactions (PPInts) are involved in almost all cellular processes. This has stimulated the development of a wide range of methods to characterize PPInts in detail. Methods with fluorescence resonance energy transfer can be technically challenging and suffer from several limitations, which could be overcome by switching to luminescence resonance energy transfer (LRET) with lanthanide ions such as Tb3+. With LRET, energy transfer between PPInt partners works over a larger distance and with less topological constraints; moreover, the long-lived luminescence of lanthanides allows one to bypass the short-lived background fluorescence...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29433909/heat-shock-protein-90-inhibitor-enhances-apoptosis-by-inhibiting-the-akt-pathway-in-thermal-stimulated-sk-mel-2-human-melanoma-cell-line
#17
Min Kyung Shin, Ki-Heon Jeong, Hyeongwon Choi, Hye-Jin Ahn, Mu-Hyoung Lee
BACKGROUND: Heat shock proteins (Hsps) are chaperone proteins, which are upregulated after various stresses. Hsp90 inhibitors have been investigated as adjuvant therapies for the treatment of melanoma. Thermal ablation could be a treatment option for surgically unresectable melanoma or congenital nevomelanocytic nevi, however, there is a limitation such as the possibility of recurrence. OBJECTIVE: We evaluated apoptosis in a melanoma cell line treated with the Hsp90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in hyperthermic conditions...
February 8, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29432501/venlafaxine-and-sertraline-does-not-affect-the-expression-of-genes-regulating-stress-response-in-female-mdd-patients
#18
Ewa Banach, Aleksandra Szczepankiewicz, Anna Leszczyńska-Rodziewicz, Joanna Pawlak, Monika Dmitrzak-Węglarz, Dorota Zaremba, Joanna Twarowska-Hauser
OBJECTIVES: The aim of this study was to analyze the expression of 3 genes involved in the regulation of HPA axis: GR, HSP90 and FKBP5, in patients with major depressive disorder (MDD) before antidepressant treatment and after 8 weeks of pharmacotherapy. Additionally, we analyzed the level of glucocorticoid receptor isoforms before and after treatment. METHODS: The study included 30 female patients (aged 18-60 years), with major depres- sive disorder diagnosed on the basis of the Structured Clinical Interview for DSM-IV (SCID)...
December 30, 2017: Psychiatria Polska
https://www.readbyqxmd.com/read/29432007/functional-role-and-hierarchy-of-the-intermolecular-interactions-in-binding-of-protein-kinase-clients-to-the-hsp90-cdc37-chaperone-structure-based-network-modeling-of-allosteric-regulation
#19
Gabrielle Stetz, Gennady M Verkhivker
A fundamental role of the Hsp90-Cdc37 chaperone machinery in mediating conformational development and activation of diverse protein kinase clients is essential for signal transduction. Structural and biochemical studies have demonstrated that characterization of global conformational changes and allosteric interactions in the Hsp90-Cdc37-kinase complexes are central to our understanding of the mechanisms underlying kinase recruitment and processing by the Hsp90-Cdc37 chaperone. The recent cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 kinase complex has provided a framework for dissecting regulatory principles underlying differentiation and recruitment of protein kinase clients to the chaperone machinery...
February 12, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29429543/effect-of-parenteral-glutamine-supplementation-combined-with-enteral-nutrition-on-hsp90-expression-and-peyer-s-patch-apoptosis-in-severely-burned-rats
#20
Jun Fan, Jing Wu, Li-Dong Wu, Bin Cheng, Shao-Yu Tao, Wei Wang, Xi Chen, Peng Zeng, Yi-Bing Wang, Qing-Yan Meng
OBJECTIVES: The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation combined with enteral nutrition (EN) on heat shock protein (Hsp) 90 expression and Peyer's patch (PP) apoptosis in severely burned rats. METHODS: Male Sprague-Dawley (SD) rats were randomly assigned to four groups: Sham burn + EN + GLN-free amino acid (AA; n = 10), sham burn + EN + GLN (n = 10), burn + EN + AA (n = 10), and burn + EN + GLN (n = 10)...
March 2018: Nutrition
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