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https://www.readbyqxmd.com/read/29035890/biocharacterization-of-heat-shock-protein-90-in-acetaminophen-treated-livers-without-conspicuous-drug-induced-liver-injury
#1
Ka Wu, Chao Guo, Min Su, Xinmou Wu, Rong Li
BACKGROUND/AIMS: Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms. Heat shock protein 90 (Hsp90) is to be expressed during various stresses, such as wound healing and tissue remodeling. Recently, it is discovered that Hsp90 is a potential modifier of cytogenesis. In comparison to clinical references of liver damage, this study was designed to assess the potential bioeffect of Hsp90 in APAP-treated livers without conspicuous drug induced liver injury (DILI)...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29032866/hsp90-maintains-boar-spermatozoa-motility-and-mitochondrial-membrane-potential-during-heat-stress
#2
V Calle-Guisado, M J Bragado, L J García-Marín, L González-Fernández
Heat Shock Proteins (HSP) is a family of proteins that protects cells from high temperatures. The present work aimed to elucidate the role that HSP90 exerts on boar sperm incubated under heat stress conditions on viability, total motility (TM), progressive motility (PM), acrosome status, mitochondrial membrane potential and plasma membrane lipid organization. Sperm were incubated in non-capacitating conditions (Tyrode's basal medium or TBM) for 3, 8 and 24h or in capacitating conditions (Tyrode's complete medium or TCM) for 4h at 38...
September 29, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/29032405/agaricus-blazei-murill-polysaccharides-protect-against-cadmium-induced-oxidative-stress-and-inflammatory-damage-in-chicken-spleens
#3
Wanqiu Xie, Ai Lv, Ruyue Li, Zequn Tang, Dexing Ma, Xiaodan Huang, Ruili Zhang, Ming Ge
Agaricus blazei Murill polysaccharide (ABP) has exhibited antioxidant and immunoregulatory activity. The aim of this study was to investigate the effect of ABP on cadmium (Cd)-induced antioxidant functions and inflammatory damage in chicken spleens. In this study, groups of 7-day-old chickens were fed with normal saline (0.2 mL single/day), CdCl2 (140 mg/kg/day), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP (140 mg/kg/day + 0.2 mL ABP). Spleens were separated on the 20th, 40th, and 60th day for each group...
October 14, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29032399/evidence-of-extracellular-vesicles-biogenesis-and-release-in-mouse-embryonic-stem-cells
#4
Lilian Cruz, Jenny Andrea Arevalo Romero, Mariana Brandão Prado, Tiago G Santos, Marilene Hohmuth Lopes
Extracellular vesicles (EVs) released by mouse embryonic stem cells (mESCs) are considered a source of bioactive molecules that modulate their microenvironment by acting on intercellular communication. Either intracellular endosomal machinery or their derived EVs have been considered a relevant system of signal circuits processing. Herein, we show that these features are found in mESCs. Ultrastructural analysis revealed structures and organelles of the endosomal system such as coated pits and endocytosis-related vesicles, prominent rough endoplasmic reticulum and Golgi apparatus, and multivesicular bodies (MVBs) containing either few or many intraluminal vesicles (ILVs) that could be released as exosomes to extracellular milieu...
October 14, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29028527/identification-and-optimization-of-novel-6-acylamino-2-aminoquinolines-as-potent-hsp90%C3%A2-c-terminal-inhibitors
#5
Fen Jiang, An-Ping Guo, Jia-Cheng Xu, Hui-Jie Wang, Xiao-Fei Mo, Qi-Dong You, Xiao-Li Xu
In order to discover novel Hsp90 inhibitors targeting the C-terminal ATP binding pocket, a novobiocin derivative based ROCS model was constructed for virtual screening. Compound 13 was identified as the lead compound and then systematical structure activity relationship (SAR) study was conducted. These efforts led to compound 69, which exhibited potent anti-proliferative activities against MCF7 and SKBr3 breast cancer cell lines. In 4T1 mice breast cancer models, 69 exhibited potent tumor growth inhibition and anti-metastasis effect...
August 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29023988/molecular-dynamics-simulation-binding-free-energy-calculation-and-unbinding-pathway-analysis-on-selectivity-difference-between-fkbp51-and-fkbp52-insight-into-the-molecular-mechanism-of-isoform-selectivity
#6
Danfeng Shi, Qifeng Bai, Shuangyan Zhou, Xuewei Liu, Huanxiang Liu, Xiaojun Yao
As co-chaperones of the 90-kDa heat shock protein(HSP90), FK506 binding protein 51 (FKBP51) and FK506 binding protein 52 (FKBP52) modulate the maturation of steroid hormone receptor through their specific FK1 domains (FKBP12-like domain 1). The inhibitors targeting FK1 domains are potential therapies for endocrine-related physiological disorders. However, the structural conservation of the FK1 domains between FKBP51 and FKBP52 make it difficult to obtain satisfactory selectivity in FK506-based drug design. Fortunately, a series of iFit ligands synthesized by Hausch et al exhibited excellent selectivity for FKBP51, providing new opportunity for design selective inhibitors...
October 12, 2017: Proteins
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#7
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29020081/heat-stress-induces-expression-of-hsp-genes-in-genetically-divergent-chickens
#8
Haniel Cedraz, Juliana Gracielle Gonzaga Gromboni, Antonio Amandio Pinto Garcia, Ronaldo Vasconcelos Farias Filho, Teillor Machado Souza, Eduardo Ribeiro de Oliveira, Elizangela Bonfim de Oliveira, Carlos Souza do Nascimento, Camila Meneghetti, Amauri Arias Wenceslau
BACKGROUND: Chickens are animals that are sensitive to thermal stress, which may decrease their production level in terms that it affects feed intake and thus, decreasing body weight gain. The Heat Shock Factors (HSF) and Heat Shock Proteins (HSP) genes are involved in the key cellular defense mechanisms during exposure in hot environments. Aimed with this study to analyze the expression of HSF1, HSF3, HSP70 and HSP90 genes in two local breeds (Peloco and Caneluda) and a commercial broiler line (Cobb 500®) to verify differences in resistance of these chicken to Heat stress treatment...
2017: PloS One
https://www.readbyqxmd.com/read/29019670/design-synthesis-and-biological-activities-of-vibsanin-b-derivatives-a-new-class-of-hsp90-c-terminal-inhibitors
#9
Li-Dong Shao, Jia Su, Baixin Ye, Jiang-Xin Liu, Zhili Zuo, Yan Li, Yue-Ying Wang, Chengfeng Xia, Qin-Shi Zhao
Previously, vibsanin B (ViB) was found to preferentially target HSP90β compared to HSP90α. In this study, multiple-experiments, including pull-down assays of biotin-ViB with recombinant HSP90β-NTD, MD, CTD, and full-length HSP90β; molecular docking of ViB and its derivatives to the HSP90 CTD; and a inhibition assay of interaction of the HSP90β CTD with GST-tagged cyclophilin 40 (Cyp40) by ViB derivatives, suggest that ViB can directly bind to the HSP90 C-terminus. Based on the docking predictions and primary structure-activity relationships (SARs), a series of ViB analogues devised with focus on the C18 position, along with compounds derivatized at the C4, C7, and C8 positions, were designed and chemically synthesized...
October 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29017502/the-presence-of-residual-gold-nanoparticles-in-samples-interferes-with-the-rt-qpcr-assay-used-for-gene-expression-profiling
#10
Natasha M Sanabria, Mary Gulumian
BACKGROUND: RT-qPCR is routinely used in expression profiling of toxicity pathway genes. However, genetic and molecular level studies used to determine, understand and clarify potential risks of engineered nanomaterials (ENMs) are still incomplete. Concerns regarding possible interference caused by intracellular ENMs during analyses have been raised. The aim of this study was to verify a qPCR procedure for gene expression assays, which can be used in toxicity and exposure assessments...
October 10, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29016855/enhanced-tau-pathology-via-ranbp9-and-hsp90-hsc70-chaperone-complexes
#11
Jung A Woo, Tian Liu, Xingyu Zhao, Courtney Trotter, Ksenia Yrigoin, Sara Cazzaro, Emilio De Narvaez, Hirah Khan, Richard Witas, Anusha Bukhari, Kamal Makati, Xinming Wang, Chad Dickey, David E Kang
Accumulation of amyloid β (Aβ) and tau represent the two major pathological hallmarks of Alzheimer's disease (AD). Despite the critical importance of Aβ accumulation as an early event in AD pathogenesis, multiple lines of evidence indicate that tau is required to mediate Aβ-induced neurotoxic signals in neurons. We have previously shown that the scaffolding protein Ran-binding protein 9 (RanBP9), which is highly elevated in brains of AD and AD mouse models, both enhances Aβ production and mediates Aβ-induced neurotoxicity...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28993342/in-vivo-detection-of-hsp90-identifies-breast-cancers-with-aggressive-behavior
#12
Takuya Osada, Kensuke Kaneko, William R Gwin, Michael A Morse, Amy Hobeika, Brian W Pogue, Zachary C Hartman, Philip F Hughes, Timothy Haystead, H Kim Lyerly
PURPOSE: Heat shock protein 90 (Hsp90), a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers (BC). We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive BC. EXPERIMENTAL DESIGN: We exploited the uptake of a Hsp90 inhibitor by malignant cells to create an imaging probe (HS131) of Hsp90 activity by linking it to a near infrared (nIR) dye. HS131 uptake into cells correlated with cell membrane expression of Hsp90 and was used to image molecular subtypes of murine and human BC in vitro and in murine models...
October 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28990809/proteomic-interrogation-of-hsp90-and-insights-for-medical-research
#13
Lorenz Weidenauer, Tai Wang, Suhasini Joshi, Gabriela Chiosis, Manfredo R Quadroni
Heat shock protein 90 (HSP90) regulates protein homeostasis in eukaryotes. As a "professional interactor", HSP90 binds to and chaperones many proteins and has both housekeeping and disease-related functions but its regulation remains in part elusive. HSP90 complexes are a target for therapy, notably against cancer, and several inhibitors are currently in clinical trials. Proteomic studies have revealed the vast interaction network of HSP90 and, in doing so, the extent of cellular processes the chaperone takes part in, especially in yeast and human cells...
October 9, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28987383/hsp90-inhibitor-nvp-auy922-enhances-the-anti-cancer-effect-of-bcl-2-inhibitor-abt-737-in-small-cell-lung-cancer-expressing-bcl-2
#14
Hannah Yang, Mi-Hee Lee, Intae Park, Hanwool Jeon, Junyoung Choi, Seyoung Seo, Sang-We Kim, Gou Young Koh, Kang-Seo Park, Dae Ho Lee
Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anticancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT-737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anticancer effects on SCLC...
October 4, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28984593/exploring-erythrocytes-as-blood-biomarkers-for-alzheimer-s-disease
#15
Anna Stevenson, Dianne Lopez, Paul Khoo, Rajesh N Kalaria, Elizabeta B Mukaetova-Ladinska
Peripheral biomarkers for dementia are few and far between. Despite research into blood plasma/serum biomarkers for dementia diagnostics, there is a lack of information on erythrocytes and their vast proteomes as potential biomarkers. This review identifies a number of relevant and potentially promising erythrocyte biomarkers for various subtypes of dementia. These include erythrocyte morphology, oxidative stress, and erythrocyte membrane proteins such as the glucose transporter (GLUT-1), amyloid-β, IgG, Hsp90, calpain-1, and band 3 protein...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28983611/suppression-by-hsp90-inhibitors-of-bmp%C3%A2-4%C3%A2-stimulated-osteoprotegerin-synthesis-in-osteoblasts-attenuation-of-p70-s6-kinase
#16
Tetsu Kawabata, Takanobu Otsuka, Kazuhiko Fujita, Shingo Kainuma, Naohiro Yamamoto, Gen Kuroyanagi, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Haruhiko Tokuda
Heat shock protein 90 (HSP90) is an ATP‑dependent ubiquitous molecular chaperon which is important in cell homeostasis. The authors previously demonstrated that bone morphogenetic protein (BMP)‑4 stimulates osteoprotegerin (OPG) production in osteoblast‑like MC3T3‑E1 cells, and that p70 S6 kinase positively regulates the OPG synthesis by BMP‑4. The present study investigated the involvement of HSP90 in the BMP‑4‑stimulated OPG synthesis and the mechanism in MC3T3‑E1 cells. HSP90 inhibitors, 17‑allylamino‑17demethoxy‑geldanamycin (17‑AAG), 17‑dimethylamino‑ethylamino‑17‑demethoxy‑geldanamycin (17‑DMAG) and geldanamycin significantly suppressed the BMP‑4‑stimulated OPG release...
September 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28980313/therapeutic-potency-of-heat-shock-protein-90-pharmacological-inhibitors-in-the-treatment-of-gastrointestinal-cancer-current-status-and-perspectives
#17
REVIEW
Nadia Boroumand, Hossein Saghi, Amir Avan, Amirhossein Bahreyni, Mikhail Ryzhikov, Majid Khazaei, Seyed Mahdi Hassanian
OBJECTIVES: Heat-shock protein-90 (HSP90) chaperone machinery is critical to the folding, stability and activity of several client proteins including many responsible for tumour initiation, progression and metastasis. Overexpression of HSP90 is correlated with poor prognosis of GI cancer. KEY FINDINGS: Pharmacological inhibitors of HSP90 suppress tumorigenic effects of HSP90 by suppressing angiogenesis, survival, metastasis and drug resistance in GI cancer. This review summarizes the role of HSP90 inhibitors in the treatment of GI cancer...
October 4, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28977641/pp32-and-set-taf-i%C3%AE-proteins-regulate-the-acetylation-of-newly-synthesized-histone-h4
#18
Francisco Saavedra, Carlos Rivera, Elizabeth Rivas, Paola Merino, Daniel Garrido, Sergio Hernández, Ignasi Forné, Isabelle Vassias, Zachary A Gurard-Levin, Iván E Alfaro, Axel Imhof, Geneviève Almouzni, Alejandra Loyola
Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade...
August 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28973376/the-integrity-and-organization-of-the-human-aipl1-functional-domains-is-critical-for-its-role-as-a-hsp90-dependent-co-chaperone-for-rod-pde6
#19
Almudena Sacristan-Reviriego, James Bellingham, Chrisostomos Prodromou, Neruban Kumaran, James Bainbridge, Michel Michaelides, Jacqueline van der Spuy
Biallelic mutations in the photoreceptor-expressed aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) are associated with autosomal recessive Leber congenital amaurosis (LCA), the most severe form of inherited retinopathy in early childhood. AIPL1 functions as a photoreceptor-specific co-chaperone that interacts with the molecular chaperone HSP90 to facilitate the stable assembly of the retinal cyclic GMP (cGMP) phosphodiesterase (PDE6) holoenzyme. In this study, we characterised the functional deficits of AIPL1 variations, some of which induce aberrant pre-mRNA AIPL1 splicing leading to the production of alternative AIPL1 isoforms...
August 26, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28972920/disrupting-effects-of-antibiotic-sulfathiazole-on-developmental-process-during-sensitive-life-cycle-stage-of-chironomus-riparius
#20
Kiyun Park, Ihn-Sil Kwak
Antibiotics in the environment are a concern due to their potential to harm humans and interrupt ecosystems. Sulfathiazole (STZ), a sulfonamide antibiotic, is commonly used in aquaculture and is typically found in aquatic ecosystems. We evaluated the ecological risk of STZ by examining biological, molecular and biochemical response in Chironomus riparius. Samples were exposed to STZ for 12, 24 and 96 h, and effects of STZ were evaluated at the molecular level by analyzing changes in gene expression related to the endocrine system, cellular stress response and enzyme activity of genes on antioxidant and detoxification pathways...
September 26, 2017: Chemosphere
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