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https://www.readbyqxmd.com/read/28337290/down-regulation-of-hsa-mir-148b-inhibits-vascular-smooth-muscle-cells-proliferation-and-migration-by-directly-targeting-hsp90-in-atherosclerosis
#1
Xinqi Zhang, Hua Shi, Yuanlin Wang, Jianxin Hu, Zhaolin Sun, Shuxiong Xu
The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are crucial pathological processes that are involved in atherosclerosis. Growing evidence suggests that microRNAs (miRNAs) play critical roles in VSMCs functions. Here, we analyzed the expression of four atherosclerosis-related miRNAs and found that hsa-miR-148b was significantly down-regulated in plaques from atherosclerotic patients compared to a healthy control group. The restoration of hsa-miR-148b function in cells transfected with a hsa-miR-148b mimicmarkedly inhibited VSMCs proliferation and migration compared to a hsa-miR-148b mimic control...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336809/lectin-galactoside-binding-soluble-3-binding-protein-promotes-17-n-allylamino-17-demethoxygeldanamycin-resistance-through-pi3k-akt-pathway-in-lung-cancer-cell-line
#2
Jong Kyu Woo, Jeong-Eun Jang, Ju-Hee Kang, Je Kyung Seong, Yeo Sung Yoon, Hyoung-Chin Kim, Sang-Jin Lee, Seun Hyun Oh
Heat shock protein 90 (HSP90) stabilizing oncoproteins has been an attractive target in cancer therapy. 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG), HSP90 inhibitor, was tested in phase II/III clinical trials, but due to lack of efficacy, clinical evaluation of 17-AAG has achieved limited success which led to resistance to 17-AAG. However, the mechanism of 17-AAG resistance has not clearly been identified. Here, we identified LGALS3BP (Lectin, galactoside-binding, soluble, 3 binding protein), a secretory glycoprotein, as a 17-AAG resistance factor...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28333289/the-role-of-daf-21-hsp90-in-mouth-form-plasticity-in-pristionchus-pacificus
#3
Bogdan Sieriebriennikov, Gabriel V Markov, Hanh Witte, Ralf J Sommer
Phenotypic plasticity is increasingly recognized to facilitate adaptive change in plants and animals, including insects, nematodes and vertebrates. Plasticity can occur as continuous or discrete (polyphenisms) variation. In social insects, e.g. in ants, some species have workers of distinct size classes while in other closely related species variation in size may be continuous. Despite the abundance of examples in nature, how discrete morphs are specified remains currently unknown. In theory, polyphenisms might require robustness, whereby the distribution of morphologies would be limited by the same mechanisms that execute buffering from stochastic perturbations, a function attributed to heat-shock proteins of the Hsp90 family...
March 13, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28330765/hsp90-and-pcreb-alterations-are-linked-to-mancozeb-dependent-behavioral-and-neurodegenerative-effects-in-a-marine-teleost
#4
Merylin Zizza, Mariana Di Lorenzo, Vincenza Laforgia, Emilia Furia, Giovanni Sindona, Marcello Canonaco, Rosa Maria Facciolo
The pesticide mancozeb (mz) is recognized as a potent inducer of oxidative stress due to its ability to catalyze the production of reactive oxygen species plus inhibiting mitochondrial respiration thus becoming an environmental risk for neurodegenerative diseases. Despite numerous toxicological studies on mz have been directed to mammals, attention on marine fish is still lacking. Thus, it was our intention to evaluate neurobehavioral activities of ornate wrasses (Thalassoma pavo) exposed to 0.2mg/l of mz after a preliminary screening test (0...
March 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28328315/analysis-of-protein-target-interactions-of-synthetic-mixtures-by-affinity-lc-ms
#5
Prachi Singh, Kalaipriya Madhaiyan, Minh-Dao Duong-Thi, Brian W Dymock, Sten Ohlson
Analysis of interactions between molecules is of fundamental importance in life science research. In this study, we applied weak affinity chromatography, based on high-performance liquid chromatography and mass spectrometry, as a powerful tool for direct analysis of the components of a chemical reaction mixture for their binding to a target protein. As a demonstration of the potential of this method, we analyzed the binding of the compounds of the reaction mixture to the chaperone heat shock protein 90 (Hsp90)...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28326005/bioactivity-of-food-peptides-biological-response-of-rats-to-bovine-milk-whey-peptides-following-acute-exercise
#6
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28324352/the-six-tomato-yellow-leaf-curl-virus-genes-expressed-individually-in-tomato-induce-different-levels-of-plant-stress-response-attenuation
#7
Rena Gorovits, Adi Moshe, Linoy Amrani, Rotem Kleinberger, Ghandi Anfoka, Henryk Czosnek
Tomato yellow leaf curl virus (TYLCV) is a begomovirus infecting tomato plants worldwide. TYLCV needs a healthy host environment to ensure a successful infection cycle for long periods. Hence, TYLCV restrains its destructive effect and induces neither a hypersensitive response nor cell death in infected tomatoes. On the contrary, TYLCV counteracts cell death induced by other factors, such as inactivation of HSP90 functionality. Suppression of plant death is associated with the inhibition of the ubiquitin 26S proteasome degradation and with a deactivation of the heat shock transcription factor HSFA2 pathways (including decreased HSP17 levels)...
March 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28320779/the-g2385r-risk-factor-for-parkinson-s-disease-enhances-chip-dependent-intracellular-degradation-of-lrrk2
#8
Iakov N Rudenko, Alice Kaganovich, Rebekah G Langston, Aleksandra Beilina, Kelechi Ndukwe, Ravindran Kumaran, Allissa A Dillman, Ruth Chia, Mark R Cookson
Autosomal dominant mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are associated with Parkinson's disease (PD). Most pathogenic LRRK2 mutations result in amino-acid substitutions in the central ROC-COR-Kinase triple domain and affect enzymatic functions of the protein. However, there are several variants in LRRK2 , including the risk factor G2385R, that impact PD pathogenesis by unknown mechanisms. Previously, we have shown that G2385R LRRK2 has decreased kinase activity in vitro and altered affinity to LRRK2 interactors...
March 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28319058/cytosolic-pkm2-stabilizes-mutant-egfr-protein-expression-through-regulating-hsp90-egfr-association
#9
Y-C Yang, T-Y Cheng, S-M Huang, C-Y Su, P-W Yang, J-M Lee, C-K Chen, M Hsiao, K-T Hua, M-L Kuo
No abstract text is available yet for this article.
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28315949/-89-zr-onartuzumab-pet-imaging-of-c-met-receptor-dynamics
#10
Martin Pool, Anton G T Terwisscha van Scheltinga, Arjan Kol, Danique Giesen, Elisabeth G E de Vries, Marjolijn N Lub-de Hooge
PURPOSE: c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of (89)Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts...
March 19, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28315162/dietary-supplementation-of-curcumin-augments-heat-stress-tolerance-through-upregulation-of-nrf-2-mediated-antioxidative-enzymes-and-hsps-in-puntius-sophore
#11
Arabinda Mahanty, Sasmita Mohanty, Bimal P Mohanty
Heat stress is one of the major environmental concerns in global warming regime and rising temperature has resulted in mass mortalities of animals including fishes. Therefore, strategies for high temperature stress tolerance and ameliorating the effects of heat stress are being looked for. In an earlier study, we reported that Nrf-2 (nuclear factor E2-related factor 2) mediated upregulation of antioxidative enzymes and heat shock proteins (Hsps) provide survivability to fish under heat stress. In this study, we have evaluated the ameliorative potential of dietary curcumin, a potential Nrf-2 inducer in heat stressed cyprinid Puntius sophore...
March 17, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28315160/modulatory-role-of-l-carnitine-against-microcystin-lr-induced-immunotoxicity-and-oxidative-stress-in-common-carp
#12
Xiu-Mei Chen, Gui-Liang Guo, Li Sun, Qiu-Shi Yang, Gui-Qin Wang, Dong-Ming Zhang
Microcystin-LR (MCLR), one of the most popular microcystins (MCs) found in many field water bodies around the world, poses great health risks to animals and humans. In the present study, healthy common carp (initial weight 24.8 ± 2.3 g) were randomly assigned to five groups. Group I was fed on normal diet as control. Group II was maintained on normal diet and received MCLR intraperitoneal injection (150 μg kg(-1) BW). Common carp in groups III, IV, and V were daily pretreated with L-carnitine (LC) at doses of 0...
March 17, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28306192/histone-deacetylase-activity-mediates-acquired-resistance-towards-structurally-diverse-hsp90-inhibitors
#13
Ryan C Chai, Jessica L Vieusseux, Benjamin J Lang, Chau H Nguyen, Michelle M Kouspou, Kara L Britt, John T Price
Heat Shock Protein 90 (HSP90) regulates multiple signaling pathways critical for tumor growth. As such, HSP90 inhibitors have been shown to act as effective anticancer agents in preclinical studies but, for a number of reasons, the same effect has not been observed in the clinical trials to date. One potential reason for this may the presence of de novo or acquired resistance within the tumors. To investigate mechanisms of resistance, we generated resistant cell lines through gradual dose escalation of the HSP90 inhibitor 17-AAG...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28302086/extracellular-hsp90-and-tgf%C3%AE-regulate-adhesion-migration-and-anchorage-independent-growth-in-a-paired-colon-cancer-cell-line-model
#14
Jo-Anne de la Mare, Tamarin Jurgens, Adrienne L Edkins
BACKGROUND: Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-β pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-β pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28301080/hsp90-inhibitor-auy922-can-reverse-fulvestrant-induced-feedback-reaction-in-human-breast-cancer-cells
#15
Jingchao Bai, Guanglin Zhou, Yufan Qiu, Yunhui Hu, Jingjing Liu, Jing Zhao, Sheng Zhang, Jin Zhang
Hormone therapy has become one of the main strategy for breast cancer, however, many estrogen receptor(ER) positive patients ends in tumor collapse due to initial or acquired resistance to hormone treatment, which includes Fulvestrant. Here we report that ErbB Receptors and downstream PI3K/AKT and ERK pathway have been reactivated after treatment of Fulvestrant in ER positive MCF-7 and T47D cells, which are related to Fulvestrant resistance. HSP90 is a universally expressed chaperone protein and plays a vital role in both normal and cancer cells, HSP90 inhibitor AUY922 can reverse this feedback reactivation effect of Fulvestrant by targeting multiple proteins related in ErbB Receptors, PI3K/AKT and ERK pathway, which is much better than single targeting inhibitors...
March 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28300840/ganetespib-synergizes-with-cyclophosphamide-to-improve-survival-of-mice-with-autochthonous-tumors-in-a-mutant-p53-dependent-manner
#16
Evguenia M Alexandrova, Sulan Xu, Ute M Moll
The DNA-alkylating cytotoxic agent cyclophosphamide (CTX) is commonly used in the clinic to treat hematological malignancies like lymphomas and leukemias as well as solid tumors, but shows dose-dependent potentially life-threatening toxicities and can induce secondary malignancies. Thus, the clinical utility of CTX would be improved if a companion drug could be identified that allows lowering the CTX dose, while maintaining or even increasing its antineoplastic therapeutic efficacy. In mouse models, high-dose CTX (300 mg/kg) is effective in treating T-lymphomas, while low dose (defined here as 100 mg/kg) is ineffective...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28298630/proteomic-analysis-of-proteome-and-histone-post-translational-modifications-in-heat-shock-protein-90-inhibition-mediated-bladder-cancer-therapeutics
#17
Qingdi Quentin Li, Jian-Jiang Hao, Zheng Zhang, L Spencer Krane, Kai H Hammerich, Thomas Sanford, Jane B Trepel, Len Neckers, Piyush K Agarwal
Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteomic study that evaluates alterations in protein expression and histone post-translational modifications (PTMs) in bladder carcinoma in response to HSP90 inhibition. We show that 5 HSP90 inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) potently inhibited the proliferation of bladder cancer 5637 cells in a dose- and time-dependent manner...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293031/genetic-variation-hsp90-shapes-human-genetic-variation
#18
Shimona Starling
No abstract text is available yet for this article.
March 15, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28291803/induction-of-hsp70-in-tumor-cells-treated-with-inhibitors-of-the-hsp90-activity-a-predictive-marker-and-promising-target-for-radiosensitization
#19
Vladimir A Kudryavtsev, Anna V Khokhlova, Vera A Mosina, Elena I Selivanova, Alexander E Kabakov
We studied a role of the inducible heat shock protein 70 (Hsp70) in cellular response to radiosensitizing treatments with inhibitors of the heat shock protein 90 (Hsp90) chaperone activity. Cell lines derived from solid tumors of different origin were treated with the Hsp90 inhibitors (17AAG, geldanamycin, radicicol, NVP-AUY922) or/and γ-photon radiation. For comparison, human cells of the non-cancerous origin were subjected to the same treatments. We found that the Hsp90 inhibitors yielded considerable radiosensitization only when they cause early and pronounced Hsp70 induction; moreover, a magnitude of radiosensitization was positively correlated with the level of Hsp70 induction...
2017: PloS One
https://www.readbyqxmd.com/read/28290541/hsp90-dependence-of-a-kinase-is-determined-by-its-conformational-landscape
#20
Qi Luo, Edgar E Boczek, Qi Wang, Johannes Buchner, Ville R I Kaila
Heat shock protein 90 (Hsp90) is an abundant molecular chaperone, involved in the folding and activation of 60% of the human kinome. The oncogenic tyrosine kinase v-Src is one of the most stringent client proteins of Hsp90, whereas its almost identical homolog c-Src is only weakly affected by the chaperone. Here, we perform atomistic molecular simulations and in vitro kinase assays to explore the mechanistic differences in the activation of v-Src and c-Src. While activation in c-Src is strictly controlled by ATP-binding and phosphorylation, we find that activating conformational transitions are spontaneously sampled in Hsp90-dependent Src mutants...
March 14, 2017: Scientific Reports
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