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Heat shock proteins

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https://www.readbyqxmd.com/read/28547731/proline-isomerization-in-the-c-terminal-region-of-hsp27
#1
T Reid Alderson, Justin L P Benesch, Andrew J Baldwin
In mammals, small heat-shock proteins (sHSPs) typically assemble into interconverting, polydisperse oligomers. The dynamic exchange of sHSP oligomers is regulated, at least in part, by molecular interactions between the α-crystallin domain and the C-terminal region (CTR). Here we report solution-state nuclear magnetic resonance (NMR) spectroscopy investigations of the conformation and dynamics of the disordered and flexible CTR of human HSP27, a systemically expressed sHSP. We observed multiple NMR signals for residues in the vicinity of proline 194, and we determined that, while all observed forms are highly disordered, the extra resonances arise from cis-trans peptidyl-prolyl isomerization about the G193-P194 peptide bond...
May 25, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#2
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28546219/inos-derived-nitric-oxide-induces-integrin-linked-kinase-endocytic-lysosome-mediated-degradation-in-the-vascular-endothelium
#3
Paula Reventun, Matilde Alique, Irene Cuadrado, Susana Marquez, Rocio Toro, Carlos Zaragoza, Marta Saura
OBJECTIVE: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. APPROACH AND RESULTS: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with inducible NO synthase knockout mice...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28543919/-heat-shock-protein-70-in-pancreatic-diseases-friend-or-foe
#4
REVIEW
Bhuwan Giri, Vrishketan Sethi, Shrey Modi, Bharti Garg, Sulagna Banerjee, Ashok Saluja, Vikas Dudeja
The heat shock response in pancreatitis that is activated via HSP70 protects acinar cells through multiple simultaneous mechanisms. It inhibits trypsinogen activation and modulates NF-κB signaling to limit acinar cell injury. On the other hand, HSP70 is overexpressed in pancreatic cancer and is hijacked by the cellular machinery to inhibit apoptosis. Inhibition of HSP70 in pancreatic cancer by a novel compound, Minnelide, has shown considerable clinical promise.
May 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28543094/mechanism-of-graphene-induced-cytotoxicity-role-of-endonucleases
#5
Tariq Fahmi, La Donna Branch, Zeid A Nima, Dae Song Jang, Alena V Savenka, Alexandru S Biris, Alexei G Basnakian
Graphene, a crystalline allotrope or carbon, presents numerous useful properties; however, its toxicity is yet to be determined. One of the most dramatic and irreversible toxic abilities of carbon nanomaterials is the induction of DNA fragmentation produced by endogenous cellular endonucleases. This study demonstrated that pristine graphene exposed to cultured kidney tubular epithelial cells is capable of inducing DNA fragmentation measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which is usually associated with cell death...
May 24, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28542473/stably-engineered-nanobubbles-and-ultrasound-an-effective-platform-for-enhanced-macromolecular-delivery-to-representative-cells-of-the-retina
#6
Sachin S Thakur, Micheal S Ward, Amirali Popat, Nicole B Flemming, Marie-Odile Parat, Nigel L Barnett, Harendra S Parekh
Herein we showcase the potential of ultrasound-responsive nanobubbles in enhancing macromolecular permeation through layers of the retina, ultimately leading to significant and direct intracellular delivery; this being effectively demonstrated across three relevant and distinct retinal cell lines. Stably engineered nanobubbles of a highly homogenous and echogenic nature were fully characterised using dynamic light scattering, B-scan ultrasound and transmission electron microscopy (TEM). The nanobubbles appeared as spherical liposome-like structures under TEM, accompanied by an opaque luminal core and darkened corona around their periphery, with both features indicative of efficient gas entrapment and adsorption, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#7
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
https://www.readbyqxmd.com/read/28542188/hsp90-inhibitors-potentiate-pgf2%C3%AE-induced-il-6-synthesis-via-p38-map-kinase-in-osteoblasts
#8
Kazuhiko Fujita, Haruhiko Tokuda, Gen Kuroyanagi, Naohiro Yamamoto, Shingo Kainuma, Tetsu Kawabata, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Takanobu Otsuka
Heat shock protein 90 (HSP90) that is ubiquitously expressed in various tissues, is recognized to be a major molecular chaperone. We have previously reported that prostaglandin F2α (PGF2α), a potent bone remodeling mediator, stimulates the synthesis of interleukin-6 (IL-6) through p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells, and that Rho-kinase acts at a point upstream of p38 MAP kinase. In the present study, we investigated the involvement of HSP90 in the PGF2α-stimulated IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28540808/exposure-to-febrile-range-hyperthermia-potentiates-wnt-signalling-and-epithelial-mesenchymal-transition-gene-expression-in-lung-epithelium
#9
Ratnakar Potla, Mohan E Tulapurkar, Irina G Luzina, Sergei P Atamas, Ishwar S Singh, Jeffrey D Hasday
BACKGROUND: As environmental and body temperatures vary, lung epithelial cells experience temperatures significantly different from normal core temperature. Our previous studies in human lung epithelium showed that: (i) heat shock accelerates wound healing and activates profibrotic gene expression through heat shock factor-1 (HSF1); (ii) HSF1 is activated at febrile temperatures (38-41 °C) and (iii) hypothermia (32 °C) activates and hyperthermia (39.5 °C) reduces expression of a subset of miRNAs that target protein kinase-Cα (PKCα) and enhance proliferation...
April 26, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28539657/using-bicistronic-constructs-to-evaluate-the-chaperone-activities-of-heat-shock-proteins-in-cells
#10
Rebecca San Gil, Tracey Berg, Heath Ecroyd
Heat shock proteins (Hsps) are molecular chaperones that prevent the aggregation of client proteins by facilitating their refolding, or trafficking them for degradation. The chaperone activities of Hsps are dependent on dynamic protein-protein interactions, including their oligomerisation into large multi-subunit complexes. Thus, tagging Hsps with fluorescent proteins can interfere with their chaperone activity. To overcome this limitation, we have exploited bicistronic constructs for the concurrent expression of a non-tagged Hsp and fluorescent reporter from a single mRNA in cells...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539411/substrate-binding-by-the-yeast-hsp110-nucleotide-exchange-factor-and-molecular-chaperone-sse1-is-not-obligate-for-its-biological-activities
#11
Veronica M Garcia, Nadinath B Nillegoda, Bernd Bukau, Kevin A Morano
The highly conserved heat-shock protein 70 (Hsp70) is a ubiquitous molecular chaperone essential for maintaining cellular protein homeostasis. The related protein Hsp110 (Sse1/Sse2 in Saccharomyces cerevisiae) functions as a nucleotide exchange factor (NEF) to regulate the protein folding activity of Hsp70. Hsp110/Sse1 can additionally prevent protein aggregation in vitro via its substrate binding domain (SBD), but the cellular roles of this "holdase" activity remain poorly defined. We generated and characterized an Sse1 mutant that separates, for the first time, its nucleotide exchange and substrate binding functions...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28537252/an-hsp90-co-chaperone-protein-in-yeast-is-functionally-replaced-by-site-specific-posttranslational-modification-in-humans
#12
Abbey D Zuehlke, Michael Reidy, Coney Lin, Paul LaPointe, Sarah Alsomairy, D Joshua Lee, Genesis M Rivera-Marquez, Kristin Beebe, Thomas Prince, Sunmin Lee, Jane B Trepel, Wanping Xu, Jill Johnson, Daniel Masison, Len Neckers
Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone. To properly chaperone its clientele, Hsp90 proceeds through an ATP-dependent conformational cycle influenced by posttranslational modifications (PTMs) and assisted by a number of co-chaperone proteins. Although Hsp90 conformational changes in solution have been well-studied, regulation of these complex dynamics in cells remains unclear. Phosphorylation of human Hsp90α at the highly conserved tyrosine 627 has previously been reported to reduce client interaction and Aha1 binding...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536652/mesencephalic-astrocyte-derived-neurotrophic-factor-reduces-cell-apoptosis-via-upregulating-hsp70-in-shsy-5y-cells
#13
Hui Sun, Ming Jiang, Xing Fu, Qiong Cai, Jingxing Zhang, Yanxin Yin, Jia Guo, Lihua Yu, Yun Jiang, Yigang Liu, Liang Feng, Zhiyu Nie, Jianmin Fang, Lingjing Jin
BACKGROUND: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress (ER stress). HSP70 family, a chaperon like heat shock protein family, was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells. However, the ER stress relative transcriptome, in MANF signaling cascades is still investigated. The involvement of HSP70, a 70kd member of HSP70 family, need further to be verified...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28536123/randomized-controlled-trial-of-mineralocorticoid-receptor-blockade-in-children-with-chronic-kidney-allograft-nephropathy
#14
Mara Medeiros, Luis Velásquez-Jones, Ana M Hernández, Guillermo Ramón-García, Saúl Valverde, Yolanda Fuentes, Arindal Vargas, Mauricio Patiño, Rosalba Pérez-Villalva, Juan Antonio Ortega-Trejo, Jonatan Barrera-Chimal, Norma A Bobadilla
BACKGROUND AND OBJECTIVES: We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1...
May 23, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28535598/antarctic-seals-molecular-biomarkers-as-indicators-for-pollutant-exposure-health-effects-and-diet
#15
K Lehnert, L Weirup, K C Harding, T Härkönen, O Karlsson, J Teilmann
Weddell (Leptonychotes weddellii), Ross (Ommatophoca rossii) and crabeater seals (Lobodon carcinophaga) are phocid seals with a circumpolar distribution around Antarctica. As long-lived and large top predators, they bioaccumulate contaminants and are considered as sentinels of ecosystem health. Antarctic seals are increasingly exposed to climate change, pollution, shipping and fisheries. To reveal and understand possible anthropogenic impacts on their immune and health status, this study investigates sensitive biomarkers of the xenobiotic metabolism and immune system in relation to mercury (Hg) burden...
May 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28535510/heat-shock-protein-a12b-protects-vascular-endothelial-cells-against-sepsis-induced-acute-lung-injury-in-mice
#16
Yi Chen, Lei Wang, Qiuxiang Kang, Xu Zhang, Guifang Yu, Xiaojian Wan, Jiafeng Wang, Keming Zhu
BACKGROUND: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. METHODS: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28533394/nanomechanics-of-the-substrate-binding-domain-of-hsp70-determine-its-allosteric-atp-induced-conformational-change
#17
Soumit Sankar Mandal, Dale R Merz, Maximilian Buchsteiner, Ruxandra I Dima, Matthias Rief, Gabriel Žoldák
Owing to the cooperativity of protein structures, it is often almost impossible to identify independent subunits, flexible regions, or hinges simply by visual inspection of static snapshots. Here, we use single-molecule force experiments and simulations to apply tension across the substrate binding domain (SBD) of heat shock protein 70 (Hsp70) to pinpoint mechanical units and flexible hinges. The SBD consists of two nanomechanical units matching 3D structural parts, called the α- and β-subdomain. We identified a flexible region within the rigid β-subdomain that gives way under load, thus opening up the α/β interface...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532230/hsp90-stabilizes-auxin-receptor-tir1-and-ensures-plasticity-of-auxin-responses
#18
Etsuko Watanabe, Shoji Mano, Ikuko Hara-Nishimura, Mikio Nishimura, Kenji Yamada
Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that facilitates the maturation of target proteins. Here, we report that the auxin receptor TIR1 is a target of cytosolic HSP90 and that HSP90 and TIR1 form a complex. Inhibition of HSP90 compromised the nuclear localization of TIR1, and abrogated plant responses to the hormone auxin. Our findings suggest that HSP90 positively regulates auxin receptor function. We also propose that HSP90 buffers or hides phenotypic variations in animals and plants by masking mutations in some of its target proteins...
May 22, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28531762/high-dose-testosterone-enanthate-supplementation-boosts-oxidative-stress-but-exerts-little-effect-on-the-antioxidant-barrier-in-sedentary-adolescent-male-rat-liver
#19
Ewa Sadowska-Krepaa, Barbara Klapcinępa, Barbara Kłapcińska, Sławomir Jagsz, Anna Nowara, Izabela Szołtysek-Bołdys, Małgorzata Chalimoniuk, Józef Langfort, Stanisław J Chrapusta
BACKGROUND: Anabolic-androgenic steroids abuse is on the rise among adolescent boys and young men, mostly in those seeking a 'shortcut' to an improved body image. This approach is associated with the risk of severe adverse health effects, some of which involve the liver and are linked to hepatic oxidative stress. Testosterone and its esters is a cornerstone of most anabolic-androgenic steroid stacking protocols. METHODS: We assessed and compared several hepatotoxicity and liver oxidative stress indices, as well as the contents of some components of the hepatic antioxidant barrier between sedentary adolescent male rats given a 6-week course of weekly im testosterone enanthate (TE, 8 or 80mg/kgBW/week) or vehicle (sesame oil) injections...
March 11, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28531761/3%C3%AE-hydroxy-urs-12-en-28-oic-acid-confers-protection-against-znonps-induced-adversity-in-caenorhabditis-elegans
#20
Hema Negi, Shilpi Khare Saikia, Ranjana Kanaujia, Satish Jaiswal, Rakesh Pandey
Despite their well reported potent risk towards human health and environment Zinc oxide nanoparticles (ZnONPs) find an extensive commercial usage due to their antimicrobial properties. Here, we evaluated the efficacy of a natural triterpene ursolic acid (3β-hydroxy-urs-12-en-28-oic acid; UA) for overcoming the cytotoxic challenges of ZnONPs employing Ceanorhabditis elegans. The 24h LC50 of Zn-ONPs (<50nm TEM) was deduced as 4.75mgL(-1). UA (25μM) was observed to defend against this toxicity by attenuating Reactive Oxygen Species (ROS) resulting into better survival at 2mgL(-1) in a time dependent behavior...
May 8, 2017: Environmental Toxicology and Pharmacology
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