The Experts below are selected from a list of 14952 Experts worldwide ranked by ideXlab platform
Nektarios Barabutis - One of the best experts on this subject based on the ideXlab platform.
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Heat shock Protein 90 inhibition in the inflamed lungs
Cell Stress and Chaperones, 2020Co-Authors: Nektarios BarabutisAbstract:Heat shock Protein 90 is a highly conserved molecular chaperone, essential for cellular survival under diverse environments. Since this Protein is employed by tumors to promote their prevalence, heat shock Protein 90 inhibitors have been developed to oppose malignancies. The anti-cancer effects of those compounds appear to be associated with anti-inflammatory properties. Thus, ongoing laborious efforts investigate the possible application of those agents towards inflammatory disorders of the lungs, such as the acute respiratory distress syndrome.
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Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock Protein 90 function
American Journal of Physiology-lung Cellular and Molecular Physiology, 2015Co-Authors: Atul Joshi, Nektarios Barabutis, Charalampos Birmpas, Christiana Dimitropoulou, Gagan Thangjam, Mary Cherian-shaw, John Dennison, John D. CatravasAbstract:Transendothelial hyperpermeability caused by numerous agonists is dependent on heat shock Protein 90 (Hsp90) and leads to endothelial barrier dysfunction (EBD). Inhibition of Hsp90 protects and res...
Shelli R. Mcalpine - One of the best experts on this subject based on the ideXlab platform.
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Redefining the Phenotype of Heat Shock Protein 90 (Hsp90) Inhibitors.
Chemistry: A European Journal, 2017Co-Authors: Yao Wang, Yen Chin Koay, Shelli R. McalpineAbstract:: The phenotypes produced when cells are treated with the heat shock Protein 90 (Hsp90) inhibitors AUY922 or 17-AAG (classical inhibitors) are different to those produced when cells are knocked down with Hsp90α. Pull-down assays using classical inhibitors suggest that these molecules bind to multiple targets other than Hsp90. Classical inhibitors also induce similar Protein markers as other anti-cancer therapies cisplatin and bortezomib that do not target Hsp90. Together these data suggest that AUY922 and 17-AAG acts on multiple targets and likely kills cells through multiple mechanisms. Comparing these classical inhibitors to the effects seen when treating cells with C-terminal Hsp90 modulators reveals that C-terminal modulators effectively bind to Hsp90, and induce phenotypic markers consistent with the Hsp90α CRISPR knockdown data. Our findings challenge the current interpretation of Hsp90 inhibitors and suggest that a large body of literature that describes the Hsp90 phenotype and inhibitors is re-examined in this context.
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The first report of direct inhibitors that target the C-terminal MEEVD region on heat shock Protein 90
Chemical Communications, 2015Co-Authors: Laura K. Buckton, H. Wahyudi, Shelli R. McalpineAbstract:Sixteen linear and cyclic peptides were designed de novo to target the C-terminus of heat shock Protein 90 (Hsp90). Protein binding data indicates that three compounds directly block co-chaperone access to Hsp90's C-terminus and luciferase renaturation assays confirm Hsp90-mediated Protein folding is disrupted. This is the first report of an inhibitor that binds directly to the C-terminal MEEVD region of Hsp90.
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Dimerization of a heat shock Protein 90 inhibitor enhances inhibitory activity
Organic and Biomolecular Chemistry, 2013Co-Authors: Hendra Wahyudi, Yao Wang, Shelli R. McalpineAbstract:Heat shock Protein 90 (hsp90) accounts for 1–2% of the total Proteins in normal cells and it functions as a dimer. Hsp90 behaves as a molecular chaperone that folds, assembles, and stabilizes client Proteins. We have developed a novel hsp90 inhibitor, and herein we describe the synthesis and biological activity of the dimerized variant of this inhibitor. Tethering a monomer inhibitor together produced a dimerized compound that more effectively inhibits hsp90 over the monomer.
Rick T Dobrowsky - One of the best experts on this subject based on the ideXlab platform.
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c terminal heat shock Protein 90 inhibitor decreases hyperglycemia induced oxidative stress and improves mitochondrial bioenergetics in sensory neurons
Journal of Proteome Research, 2012Co-Authors: Lizhi Zhang, Huiping Zhao, Brian S J Blagg, Rick T DobrowskyAbstract:Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in which hyperglycemia-induced mitochondrial dysfunction and enhanced oxidative stress contribute to sensory neuron pathology. KU-32 is a novobiocin-based, C-terminal inhibitor of the molecular chaperone, heat shock Protein 90 (Hsp90). KU-32 ameliorates multiple sensory deficits associated with the progression of DPN and protects unmyelinated sensory neurons from glucose-induced toxicity. Mechanistically, KU-32 increased the expression of Hsp70, and this Protein was critical for drug efficacy in reversing DPN. However, it remained unclear if KU-32 had a broader effect on chaperone induction and if its efficacy was linked to improving mitochondrial dysfunction. Using cultures of hyperglycemically stressed primary sensory neurons, the present study investigated whether KU-32 had an effect on the translational induction of other chaperones and improved mitochondrial oxidative stress and bioenergetics. A variation of stable isotope labe...
Hugo Fasold - One of the best experts on this subject based on the ideXlab platform.
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Isolation and quantification of the heat shock Protein 90 alpha and beta isoforms from rat liver.
Protoplasma, 2020Co-Authors: Thomas Langer, Hugo FasoldAbstract:Heat shock Protein 90 (Hsp90) is an abundant cytosolic Protein. In higher eukaryotes two isoforms of Hsp90 exist, Hsp90α and Hsp90β. Hsp90 was purified from rat liver and after sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a double band at about 90 kDa. The two bands were separated and identified as the Hsp90α and Hsp90β isoforms. There was no entry in the Protein databases for the Hsp90α isoform from rat. Furthermore, the ratio of the two Hsp90 isoforms was determined.
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Isolation and quantification of the heat shock Protein 90 alpha and beta isoforms from rat liver.
Protoplasma, 2020Co-Authors: Thomas Langer, Hugo FasoldAbstract:Heat shock Protein 90 (Hsp90) is an abundant cytosolic Protein. In higher eukaryotes two isoforms of Hsp90 exist, Hsp90 alpha and Hsp90 beta. Hsp90 was purified from rat liver and after sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a double band at about 90 kDa. The two bands were separated and identified as the Hsp90 alpha and Hsp90 beta isoforms. There was no entry in the Protein databases for the Hsp90 alpha isoform from rat. Furthermore, the ratio of the two Hsp90 isoforms was determined.
Jay L Zweier - One of the best experts on this subject based on the ideXlab platform.
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heat shock Protein 90 augments neuronal nitric oxide synthase activity by enhancing ca2 calmodulin binding
Biochemical Journal, 2001Co-Authors: Yao Song, Jay L ZweierAbstract:: Heat-Shock Protein 90 (hsp90) has been shown to facilitate neuronal NO synthase (nNOS, type 1) activity in vivo. But the direct effect of hsp90 on purified nNOS has not been determined yet. Moreover, the mechanism underlying the action of hsp90 is not known. nNOS activity is primarily initiated and regulated by the binding of Ca(2+)/calmodulin (CaM). Therefore, we explored whether hsp90 modulates nNOS activity by affecting CaM binding. Recombinant rat nNOS was purified from the stably transfected cells by affinity chromatography. hsp90 increased nNOS activity in a dose-dependent manner with an EC(50) of 24.1+/-6.4 nM. In the presence of hsp90, the CaM-nNOS dose-response curve was shifted markedly to the left and the maximal activity was also elevated. Further in vitro Protein-binding experiments confirmed that hsp90 increased the binding of CaM to nNOS. Taken together, these data indicate that hsp90 directly augments nNOS catalytic function and that this effect is, at least partially, mediated by CaM-binding enhancement.