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https://www.readbyqxmd.com/read/29141220/phosphorylation-and-ubiquitination-regulate-protein-phosphatase-5-activity-and-its-prosurvival-role-in-kidney-cancer
#1
Natela Dushukyan, Diana M Dunn, Rebecca A Sager, Mark R Woodford, David R Loiselle, Michael Daneshvar, Alexander J Baker-Williams, John D Chisholm, Andrew W Truman, Cara K Vaughan, Timothy A Haystead, Gennady Bratslavsky, Dimitra Bourboulia, Mehdi Mollapour
The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity. Here, we show an "on/off switch" mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29139182/deep-level-defect-enhanced-photothermal-performance-of-bismuth-sulfide-gold-heterojunction-nanorods-for-ct-imaging-guided-photothermal-therapy-of-cancer
#2
Yan Cheng, Yun Chang, Yanlin Feng, Hui Jian, Zhaohui Tang, Haiyuan Zhang
Bismuth sulfide (Bi2S3) nanomaterials are emerging as a promising theranostic platform for CT imaging and photothermal therapy of cancer. Herein, the photothermal property of Bi2S3 nanorods (NRs) was unveiled to intensely correlate to their intrinsic deep level defects (DLDs) that potentially could work as electron-hole nonradiative recombination centers to promote phonon production, ultimately leading to photothermal performance. Bi2S3-Au heterojunction NRs were designed to hold more significant DLD property, exhibiting more potent photothermal performance than Bi2S3 NRs...
November 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29138676/resveratrol-modulation-of-protein-expression-in-parkin-mutant-human-skin-fibroblasts-a-proteomic-approach
#3
Daniele Vergara, Antonio Gaballo, Anna Signorile, Anna Ferretta, Paola Tanzarella, Consiglia Pacelli, Marco Di Paola, Tiziana Cocco, Michele Maffia
In this study, we investigated by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) analysis the effects of resveratrol treatment on skin primary fibroblasts from a healthy subject and from a parkin-mutant early onset Parkinson's disease patient. Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson's disease. Functional alteration of parkin leads to impairment of the ubiquitin-proteasome system, resulting in the accumulation of misfolded or aggregated proteins accountable for the neurodegenerative process...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29137866/development-of-noviomimetics-that-modulate-molecular-chaperones-and-manifest-neuroprotective-effects
#4
Leah K Forsberg, Mercy Anyika, Zhenyuan You, Sean Emery, Mason McMullen, Rick T Dobrowsky, Brian S J Blagg
Heat shock protein 90 (Hsp90) is a chaperone under investigation for the treatment of cancer and neurodegenerative diseases. Neuroprotective Hsp90 C-terminal inhibitors derived from novobiocin (novologues) include KU-32 and KU-596. These novologues modulate molecular chaperones and result in an induction of Heat Shock Protein 70 (Hsp70). "Noviomimetics" replace the synthetically complex noviose sugar with a simple cyclohexyl moiety to maintain biological efficacy as compared to novologues KU-596 and KU-32...
October 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29137485/heat-stress-prevents-the-decrease-in-succinate-dehydrogenase-activity-in-the-extensor-digitorum-longus-of-streptozotocin-induced-diabetic-rats
#5
K Nonaka, S Une, M Komatsu, R Yamaji, J Akiyama
This study aimed to investigate whether heat stress (HS) prevents a decrease in succinate dehydrogenase (SDH) activity and heat shock protein 60 (HSP60) and superoxide dismutase 2 (SOD2) contents in the extensor digitorum longus of streptozotocin (STZ)-induced diabetic rats. Twelve-week-old male Wistar rats were assigned to one of the four groups (n=6/group): control (Con), HS, diabetes mellitus (DM), and diabetes mellitus and heat stress (DM+HS). Diabetes was induced by the administration of STZ (50 mg/kg)...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29137250/molecular-chaperones-in-the-acquisition-of-cancer-cell-chemoresistance-with-mutated-tp53-and-mdm2-up-regulation
#6
Zuzanna Tracz-Gaszewska, Marta Klimczak, Przemyslaw Biecek, Marcin Herok, Marcin Kosinski, Maciej B Olszewski, Patrycja Czerwińska, Milena Wiech, Maciej Wiznerowicz, Alicja Zylicz, Maciej Zylicz, Bartosz Wawrzynow
Utilizing the TCGA PANCAN12 dataset we discovered that cancer patients with mutations in TP53 tumor suppressor and overexpression of MDM2 oncogene exhibited decreased survival post treatment. Interestingly, in the case of breast cancer patients, this phenomenon correlated with high expression level of several molecular chaperones belonging to the HSPA, DNAJB and HSPC families. To verify the hypothesis that such a genetic background may promote chaperone-mediated chemoresistance, we employed breast and lung cancer cell lines that constitutively overexpressed heat shock proteins and have shown that HSPA1A/HSP70 and DNAJB1/HSP40 facilitated the binding of mutated p53 to the TAp73α protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136820/fluorescent-ligand-fishing-combination-with-in-situ-imaging-and-characterizing-to-screen-hsp-90-inhibitors-from-curcuma-longa-l-based-on-inp-zns-quantum-dots-embedded-mesoporous-nanoparticles
#7
Yue Hu, Anchen Fu, Zhaoyi Miao, Xiaojing Zhang, Tianlin Wang, An Kang, Jinjun Shan, Dong Zhu, Wei Li
Although ligand fishing has been shown to be an efficient technique for the identification of bioactive components from complex mixtures such as natural products, it cannot be applied to biomedical image processing. Herein, a specific fluorescent ligand fishing combined with in situ imaging approach is presented for the identification of heat shock protein 90 (Hsp 90) inhibitors from complex matrixes, Curcuma longa L., using N-terminus immobilized Hsp 90α functionalized InP/ZnS quantum dots embedded mesoporous nanoparticles (i...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29136455/lbh589-inhibits-glioblastoma-growth-and-angiogenesis-through-suppression-of-hif-1%C3%AE-expression
#8
Zhi-Gang Yao, Wen-Huan Li, Fang Hua, Hong-Xia Cheng, Miao-Qing Zhao, Xi-Chao Sun, Ye-Jun Qin, Jia-Mei Li
Glioblastoma (GBM) is an angiogenic malignancy with a highly unfavorable prognosis. Angiogenesis in GBM represents an adaptation to a hypoxic microenvironment and is correlated with tumor growth, invasion, clinical recurrence, and lethality. LBH589 (also called panobinostat) is a histone deacetylase (HDAC) inhibitor with potent antitumor activity. In the current study, we investigated the mechanism and effects of LBH589 on GBM growth and hypoxia-induced angiogenesis in vitro and in vivo. To determine the antitumor and angiogenesis activity and mechanism of LBH589, we used cell proliferations in vitro and GBM xenografts in vivo...
December 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29135941/the-small-heat-shock-protein-%C3%AE-crystallin-b-shows-neuroprotective-properties-in-a-glaucoma-animal-model
#9
Fabian Anders, Aiwei Liu, Carolina Mann, Julia Teister, Jasmin Lauzi, Solon Thanos, Franz H Grus, Norbert Pfeiffer, Verena Prokosch
Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC) loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP), followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29135937/relax-cool-down-and-scaffold-how-to-restore-surface-expression-of-folding-deficient-mutant-gpcrs-and-slc6-transporters
#10
REVIEW
H M Mazhar Asjad, Shahrooz Nasrollahi-Shirazi, Sonja Sucic, Michael Freissmuth, Christian Nanoff
Many diseases arise from mutations, which impair protein folding. The study of folding-deficient variants of G protein-coupled receptors and solute carrier 6 (SLC6) transporters has shed light on the folding trajectory, how it is monitored and how misfolding can be remedied. Reducing the temperature lowers the energy barrier between folding intermediates and thereby eliminates stalling along the folding trajectory. For obvious reasons, cooling down is not a therapeutic option. One approach to rescue misfolded variants is to use membrane-permeable orthosteric ligands...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29135234/evaluating-the-effect-of-phosphorylation-on-the-structure-and-dynamics-of-hsp27-dimers-by-means-of-ion-mobility-mass-spectrometry
#11
Blagojce Jovcevski, Megan A Kelly, J Andrew Aquilina, Justin L P Benesch, Heath Ecroyd
The quaternary structure and dynamics of the human small heat-shock protein Hsp27 is linked to its molecular chaperone function and influenced by post-translational modifications, including phosphorylation. Phosphorylation of Hsp27 promotes oligomer dissociation and can enhance chaperone activity. This study explored the impact of phosphorylation on the quaternary structure and dynamics of Hsp27. Using mutations that mimic phosphorylation and ion mobility mass spectrometry we show that successive substitutions result in an increase in the conformational heterogeneity of Hsp27 dimers...
November 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29134130/recent-progress-in-the-research-of-cold-inducible-rna-binding-protein
#12
REVIEW
Peng Zhong, He Huang
Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein which can be induced after exposure to a moderate cold-shock in different species ranging from amphibians to humans. Expression of CIRP can also be regulated by hypoxia, UV radiation, glucose deprivation, heat stress and H2O2, suggesting that CIRP is a general stress-response protein. In response to stress, CIRP can migrate from the nucleus to the cytoplasm and regulate mRNA stability through its binding site on the 3'-UTR of its targeted mRNAs...
November 2017: Future Science OA
https://www.readbyqxmd.com/read/29133339/decreased-ceramide-underlies-mitochondrial-dysfunction-in-charcot-marie-tooth-2f
#13
Nicholas U Schwartz, Ryan W Linzer, Jean-Philip Truman, Mikhail Gurevich, Yusuf A Hannun, Can E Senkal, Lina M Obeid
Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurologic disorder, but its molecular mechanisms remain unclear. One variant of CMT, 2F, is characterized by mutations in heat shock protein 27 (Hsp27). As bioactive sphingolipids have been implicated in neurodegenerative diseases, we sought to determine if their dysregulation is involved in CMT. Here, we show that Hsp27 knockout mice demonstrated decreases in ceramide in peripheral nerve tissue and that the disease-associated Hsp27 S135F mutant demonstrated decreases in mitochondrial ceramide...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29132139/study-of-hspb6-insights-into-the-properties-of-the-multifunctional-protective-agent
#14
Fazhao Li, Han Xiao, Fangfang Zhou, Zhiping Hu, Binbin Yang
HSPB6(Heat shock protein B6), is also referred to as P20/HSP20. Unlike other many other members of sHSP(small Heat shock protein) family, which tend to form high-molecular-mass oligomers, in solution, human HSPB6 only forms dimers. However, it still exhibits chaperon-like activity comparable with that of HSPB5. It is expressed ubiquitously, with high and constitutive expression in muscular tissues. sHSPs characteristically function as molecular chaperones and HSPB6 also has a molecular chaperone activity. HSPB6 is up-regulated in response to diverse cellular stress or damage and protect cells from otherwise lethal conditions...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29132006/ocean-acidification-dampens-physiological-stress-response-to-warming-and-contamination-in-a-commercially-important-fish-argyrosomus-regius
#15
Eduardo Sampaio, Ana R Lopes, Sofia Francisco, Jose R Paula, Marta Pimentel, Ana L Maulvault, Tiago Repolho, Tiago F Grilo, Pedro Pousão-Ferreira, António Marques, Rui Rosa
Increases in carbon dioxide (CO2) and other greenhouse gases emissions are changing ocean temperature and carbonate chemistry (warming and acidification, respectively). Moreover, the simultaneous occurrence of highly toxic and persistent contaminants, such as methylmercury, will play a key role in further shaping the ecophysiology of marine organisms. Despite recent studies reporting mostly additive interactions between contaminant and climate change effects, the consequences of multi-stressor exposure are still largely unknown...
November 10, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29131867/differential-transcriptome-analysis-reveals-genes-related-to-cold-tolerance-in-seabuckthorn-carpenter-moth-eogystia-hippophaecolus
#16
Mingming Cui, Ping Hu, Tao Wang, Jing Tao, Shixiang Zong
Seabuckthorn carpenter moth, Eogystia hippophaecolus (Lepidoptera: Cossidae), is an important pest of sea buckthorn (Hippophae rhamnoides), which is a shrub that has significant ecological and economic value in China. E. hippophaecolus is highly cold tolerant, but limited studies have been conducted to elucidate the molecular mechanisms underlying its cold resistance. Here we sequenced the E. hippophaecolus transcriptome using RNA-Seq technology and performed de novo assembly from the short paired-end reads...
2017: PloS One
https://www.readbyqxmd.com/read/29131521/high-hsf4-expression-is-an-independent-indicator-of-poor-overall-survival-and-recurrence-free-survival-in-patients-with-primary-colorectal-cancer
#17
Yingchi Yang, Lan Jin, Jinghui Zhang, Jin Wang, Xiaomu Zhao, Guocong Wu, Hongwei Yao, Zhongtao Zhang
Heat shock factor 4 (HSF4) is a member of the HSF family. In this study, by using data from the Cancer Genome Atlas-Colorectal Cancer (TCGA-CRC), we investigated the expression profile and the prognostic value of the HSF4 in terms of overall survival (OS) and recurrence free survival (RFS) in CRC patients. RNA-Seq data showed that HSF4 RNA expression was significantly higher in CRC tissues (N = 380) than in the corresponding normal tissues (N = 51) (mean ± SD: 3.56 ± 1.28 vs. 1.85 ± 0...
November 13, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29129721/immunological-considerations-underlying-heat-shock-protein-mediated-cancer-vaccine-strategies
#18
REVIEW
Mathew Kelly, Douglas McNeel, Paul Fisch, Miroslav Malkovsky
The success of active immunotherapies in the prevention of many infectious diseases over the course of over 200 years has lead scientists to wonder if the same principles could be applied to cancer. Antigen-specific active immunotherapies for the treatment of cancer have been researched for over two decades, however, the overwhelming majority of these studies have failed to stimulate robust clinical responses. It is clear that current active immunotherapy research should incorporate methods to increase the immunostimulatory capacity of these therapies...
November 9, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29129702/fkbp8-protects-the-heart-from-hemodynamic-stress-by-preventing-the-accumulation-of-misfolded-proteins-and-endoplasmic-reticulum-associated-apoptosis-in-mice
#19
Tomofumi Misaka, Tomokazu Murakawa, Kazuhiko Nishida, Yosuke Omori, Manabu Taneike, Shigemiki Omiya, Chris Molenaar, Yoshihiro Uno, Osamu Yamaguchi, Junji Takeda, Ajay M Shah, Kinya Otsu
Protein quality control in cardiomyocytes is crucial to maintain cellular homeostasis. The accumulation of damaged organelles, such as mitochondria and misfolded proteins in the heart is associated with heart failure. During the process to identify novel mitochondria-specific autophagy (mitophagy) receptors, we found FK506-binding protein 8 (FKBP8), also known as FKBP38, shares similar structural characteristics with a yeast mitophagy receptor, autophagy-related 32 protein. However, knockdown of FKBP8 had no effect on mitophagy in HEK293 cells or H9c2 myocytes...
November 9, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29128340/the-interaction-between-a-hsp-70-gene-variant-with-dietary-calories-in-determining-serum-markers-of-inflammation-and-cardiovascular-risk
#20
Mehrane Mehramiz, Seyed Mahdi Hassanian, Maryam Mardan-Nik, Alireza Pasdar, Khadijeh Jamialahmadi, Hamid Fiuji, Mehrdad Moetamani-Ahmadi, Seyed Mohammad Reza Parizadeh, Mohsen Moohebati, Alireza Heidari-Bakavoli, Mahmoud Ebrahimi, Gordon A Ferns, Majid Ghayour-Mobarhan, Amir Avan
BACKGROUND: The high prevalence of cardiovascular disease (CVD) globally is attributable to an interaction between environmental and genetic factors. Gene × diet interaction studies aim to explore how a modifiable factor interacts with genetic predispositions. Here we have explored the interaction of a heat shock protein (HSP70) gene polymorphism (+1267A > G) with dietary intake and their possible association with serum C-reactive protein (CRP), an inflammatory marker, that is a major component of CVD risk...
October 24, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
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