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Protein aggregation

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https://www.readbyqxmd.com/read/28212571/activation-of-jnk-and-ire1-is-critically-involved-in-tanshinone-i-induced-p62-dependent-autophagy-in-malignant-pleural-mesothelioma-cells-implication-of-p62-uba-domain
#1
Jihyun Lee, Eun Jung Sohn, Sangwook Yoon, Gunho Won, Chang Geun Kim, Ji Hoon Jung, Sung-Hoon Kim
The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211847/syntrophic-linkage-between-predatory-carpediemonas-and-specific-prokaryotic-populations
#2
Emmo Hamann, Halina E Tegetmeyer, Dietmar Riedel, Sten Littmann, Soeren Ahmerkamp, Jianwei Chen, Philipp F Hach, Marc Strous
Most anoxic environments are populated by small (<10 μm) heterotrophic eukaryotes that prey on different microbial community members. How predatory eukaryotes engage in beneficial interactions with other microbes has rarely been investigated so far. Here, we studied an example of such an interaction by cultivating the anerobic marine flagellate, Carpediemonas frisia sp. nov. (supergroup Excavata), with parts of its naturally associated microbiome. This microbiome consisted of so far uncultivated members of the Deltaproteobacteria, Bacteroidetes, Firmicutes, Verrucomicrobia and Nanoarchaeota...
February 17, 2017: ISME Journal
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#3
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28208397/impact-of-lipid-rafts-on-the-t-cell-receptor-and-peptide-major-histocompatibility-complex-interactions-under-different-measurement-conditions
#4
Long Li, Guang-Kui Xu, Fan Song
The interactions between T-cell receptor (TCR) and peptide-major-histocompatibility complex (pMHC), which enable T-cell development and initiate adaptive immune responses, have been intensively studied. However, a central issue of how lipid rafts affect the TCR-pMHC interactions remains unclear. Here, by using a statistical-mechanical membrane model, we show that the binding affinity of TCR and pMHC anchored on two apposing cell membranes is significantly enhanced because of the lipid raft-induced signaling protein aggregation...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28208081/molecular-synergy-in-biolubrication-the-role-of-cartilage-oligomeric-matrix-protein-comp-in-surface-structuring-of-lubricin
#5
Akanksha Raj, Min Wang, Chao Liu, Liaquat Ali, Niclas G Karlsson, Per M Claesson, Andra Dėdinaitė
HYPOTHESIS: Synovial surfaces are lubricated by biomolecular aggregates that act in synergy, and lubricin is one key biolubricant. Its molecular structure allows extensive hydration and this is conducive to its lubrication performance. However, in order to fullfil its lubrication function it needs to be anchored and oriented on the surface in a proper way. We suggest that cartilage oligomeric matrix protein (COMP) is one of the biomolecules that promotes anchoring of lubricin in a fashion that facilitates lubrication...
February 8, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28208072/identification-of-triosephosphate-isomerase-as-a-novel-allergen-in-octopus-fangsiao
#6
Yang Yang, Zhong-Wei Chen, Barry K Hurlburt, Gui-Ling Li, Yong-Xia Zhang, Dan-Xia Fei, Hai-Wang Shen, Min-Jie Cao, Guang-Ming Liu
Octopus is an important mollusk in human dietary for its nutritional value, however it also causes allergic reactions in humans. Major allergens from octopus have been identified, while the knowledge of novel allergens remains poor. In the present study, a novel allergen with molecular weight of 28kDa protein was purified from octopus (Octopus fangsiao) and identified as triosephosphate isomerase (TIM) by mass spectrometry. TIM aggregated beyond 45°C, and its IgE-binding activity was affected under extreme pH conditions due to the altered secondary structure...
February 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28208059/designer-protein-disaggregases-to-counter-neurodegenerative-disease
#7
REVIEW
James Shorter
Protein misfolding and aggregation unify several devastating neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. There are no effective therapeutics for these disorders and none that target the reversal of the aberrant protein misfolding and aggregation that cause disease. Here, I showcase important advances to define, engineer, and apply protein disaggregases to mitigate deleterious protein misfolding and counter neurodegeneration. I focus on two exogenous protein disaggregases, Hsp104 from yeast and gene 3 protein from bacteriophages, as well as endogenous human protein disaggregases, including: (a) Hsp110, Hsp70, Hsp40, and small heat-shock proteins; (b) HtrA1; and (c) NMNAT2 and Hsp90...
February 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28207877/selective-inhibition-of-aggregation-fibrillation-of-bovine-serum-albumin-by-osmolytes-mechanistic-and-energetics-insights
#8
Moumita Dasgupta, Nand Kishore
Bovine serum albumin (BSA) is an important transport protein of the blood and its aggregation/fibrillation would adversely affect its transport ability leading to metabolic disorder. Therefore, understanding the mechanism of fibrillation/aggregation of BSA and design of suitable inhibitor molecules for stabilizing its native conformation, are of utmost importance. The qualitative and quantitative aspects of the effect of osmolytes (proline, hydroxyproline, glycine betaine, sarcosine and sorbitol) on heat induced aggregation/fibrillation of BSA at physiological pH (pH 7...
2017: PloS One
https://www.readbyqxmd.com/read/28207746/protease-resistance-of-infectious-prions-is-suppressed-by-removal-of-a-single-atom-in-the-cellular-prion-protein
#9
Henning Leske, Simone Hornemann, Uli Simon Herrmann, Caihong Zhu, Paolo Dametto, Bei Li, Florent Laferriere, Magdalini Polymenidou, Pawel Pelczar, Regina Rose Reimann, Petra Schwarz, Elisabeth Jane Rushing, Kurt Wüthrich, Adriano Aguzzi
Resistance to proteolytic digestion has long been considered a defining trait of prions in tissues of organisms suffering from transmissible spongiform encephalopathies. Detection of proteinase K-resistant prion protein (PrPSc) still represents the diagnostic gold standard for prion diseases in humans, sheep and cattle. However, it has become increasingly apparent that the accumulation of PrPSc does not always accompany prion infections: high titers of prion infectivity can be reached also in the absence of protease resistant PrPSc...
2017: PloS One
https://www.readbyqxmd.com/read/28207419/both-genome-and-cytosol-dynamics-change-in-e-coli-challenged-with-sublethal-rifampicin
#10
Michal Wlodarski, Bianca Raciti, Jurij Kotar, Marco Cosentino Lagomarsino, Gillian M Fraser, Pietro Cicuta
While the action of many antimicrobial drugs is well understood at the molecular level, a systems-level physiological response to antibiotics remains largely unexplored. This work considers fluctuation dynamics of both the chromosome and cytosol in Escherichia coli, and their response to sublethal treatments of a clinically important antibiotic, rifampicin. We precisely quantify the changes in dynamics of chromosomal loci and cytosolic aggregates (a rheovirus nonstructural protein known as μNS-GFP), measuring short time-scale displacements across several hours of drug exposure...
February 16, 2017: Physical Biology
https://www.readbyqxmd.com/read/28206769/extensive-chemical-modifications-in-the-primary-protein-structure-of-igg1-subvisible-particles-are-necessary-for-breaking-immune-tolerance
#11
Bjoern Boll, Juliana Bessa, Emilien Folzer, Anacelia Ríos Quiroz, Roland Schmidt, Patrick Bulau, Christof Finkler, Hanns-Christian Mahler, Jörg Huwyler, Antonio Iglesias, Atanas V Koulov
A current concern with the use of therapeutic proteins is the likely presence of aggregates and submicron, subvisible and visible particles. It has been proposed that aggregates and particles may lead to unwanted increases in immune response with a possible impact on safety or efficacy. The aim of this study was thus to evaluate the ability of subvisible particles of a therapeutic antibody to break immune tolerance in an IgG1 transgenic mouse model and to understand the particle attributes that may play a role in this process...
February 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28205434/recent-advances-on-magnetic-relaxation-switching-assay-based-nanosensors
#12
Yang Zhang, Hong Yang, Zhiguo Zhou, Kai Huang, Shi-Ping Yang, Gang Han
Magnetic relaxation switching assay (MRSw)-based nanosensors respond to the changes of transverse relaxation time (T2) of water molecules resulted from the analyte-induced aggregation / disaggregation of magnetic nanoparticles (MNPs). This strategy has been widely applied to the detections of various substrates from heavy metal ions to organic pollutants, proteins, nucleic acids, bacteria/viruses, and specific cells. Compared with other nanosensors, MRSw-based nanosensors not only are free from the background interferences, signal bleaching, and quenching but also overcome light scattering from samples without pre-treatments...
February 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28204843/bread-wheat-milling-behavior-effects-of-genetic-and-environmental-factors-and-modeling-using-grain-mechanical-resistance-traits
#13
François-Xavier Oury, P Lasme, C Michelet, A Dubat, O Gardet, E Heumez, B Rolland, M Rousset, J Abecassis, C Bar L'Helgouac'h, V Lullien-Pellerin
Genetic (Pinb-D1 alleles) and environment (through vitreousness) have important effects on bread wheat milling behavior. SKCS optimal values corresponding to soft vitreous or hard mealy grains were defined to obtain the highest total flour yield. Near-isogenic lines of bread wheat that differ in hardness, due to distinct puroindoline-b alleles (the wild type, Pinb-D1a, or the mutated forms, Pinb-D1b or Pinb-D1d), were grown in different environments and under two nitrogen fertilization levels, to study genetic and environmental effects on milling behavior...
February 15, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/28203481/lens-endogenous-peptide-%C3%AE-a66-80-generates-hydrogen-peroxide-and-induces-cell-apoptosis
#14
Murugesan Raju, Puttur Santhoshkumar, K Krishna Sharma
In previous studies, we reported the presence of a large number of low-molecular-weight (LMW) peptides in aged and cataract human lens tissues. Among the LMW peptides, a peptide derived from αA-crystallin, αA66-80, was found in higher concentration in aged and cataract lenses. Additional characterization of the αA66-80 peptide showed beta sheet signature, and it formed well-defined unbranched fibrils. Further experimental data showed that αA66-80 peptide binds α-crystallin, impairs its chaperone function, and attracts additional crystallin proteins to the peptide α-crystallin complex, leading to the formation of larger light scattering aggregates...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28202670/mechanisms-of-lrrk2-dependent-neurodegeneration-role-of-enzymatic-activity-and-protein-aggregation
#15
REVIEW
Md Shariful Islam, Darren J Moore
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD) with autosomal dominant inheritance. Accordingly, LRRK2 has emerged as a promising therapeutic target for disease modification in PD. Since the first discovery of LRRK2 mutations some 12 years ago, LRRK2 has been the subject of intense investigation. It has been established that LRRK2 can function as a protein kinase, with many putative substrates identified, and can also function as a GTPase that may serve in part to regulate kinase activity...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202663/translating-protein-phosphatase-research-into-treatments-for-neurodegenerative-diseases
#16
REVIEW
Jeyapriya R Sundaram, Irene C J Lee, Shirish Shenolikar
Many of the major neurodegenerative disorders are characterized by the accumulation of intracellular protein aggregates in neurons and other cells in brain, suggesting that errors in protein quality control mechanisms associated with the aging process play a critical role in the onset and progression of disease. The increased understanding of the unfolded protein response (UPR) signaling network and, more specifically, the structure and function of eIF2α phosphatases has enabled the development or discovery of small molecule inhibitors that show great promise in restoring protein homeostasis and ameliorating neuronal damage and death...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202413/engineered-antibody-ch2-domains-binding-to-nucleolin-isolation-characterization-and-improvement-of-aggregation
#17
De-Zhi Li, Rui Gong, Jun Zheng, Xi-Hai Chen, Dimiter S Dimitrov, Qi Zhao
Smaller recombinant antibody fragments are now emerging as alternatives of conventional antibodies. Especially, immunoglobulin (Ig) constant CH2 domain and engineered CH2 with improved stability are promising as scaffolds for selection of specific binders to various antigens. We constructed a yeast display library based on an engineered human IgG1 CH2 scaffold with diversified loop regions. A group of CH2 binders were isolated from this yeast display library by panning against nucleolin, which is a tumor-associated antigen involved in cell proliferation, tumor cell growth and angiogenesis...
February 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28202389/targeting-the-hdac2-hnf-4a-mir-101b-ampk-pathway-rescues-tauopathy-and-dendritic-abnormalities-in-alzheimer-s-disease
#18
Dan Liu, Hui Tang, Xin-Yan Li, Man-Fei Deng, Na Wei, Xiong Wang, Ya-Fan Zhou, Ding-Qi Wang, Peng Fu, Jian-Zhi Wang, Sébastien S Hébert, Jian-Guo Chen, Youming Lu, Ling-Qiang Zhu
Histone deacetylase 2 (HDAC2) plays a major role in the epigenetic regulation of gene expression. Previous studies have shown that HDAC2 expression is strongly increased in Alzheimer's disease (AD), a major neurodegenerative disorder and the most common form of dementia. Moreover, previous studies have linked HDAC2 to Aβ overproduction in AD; however, its involvement in tau pathology and other memory-related functions remains unclear. Here, we show that increased HDAC2 levels strongly correlate with phosphorylated tau in a mouse model of AD...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28201963/inhibition-of-amyloid-like-fibril-formation-of-trypsin-by-red-wines
#19
Márta Kotormán, Phanindra Babu Kasi, László Halász, Attila Borics
The aim of the present study was to examine the potential role and applicability of dietary supplements in reducing the risk of development of amyloid diseases associated with the gastrointestinal tract, such as type II diabetes. Trypsin, a well-known serine protease was used as a model protein in our experiments. The effect of various red wines on the formation of amyloid-like fibrils of trypsin was studied in vitro, in aqueous ethanol, at pH 7.0. Turbidity measurements, aggregation kinetics experiments, Congo red binding assays and electronic circular dichroism spectroscopic measurements were used to follow the aggregation process in the presence or absence of various red wines...
February 14, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28199195/tissue-transglutaminase-tg2-and-mitochondrial-function-and-dysfunction
#20
Thung-S Lai, Cheng-Jui Lin, Yu-Ting Wu, Chih-Jen Wu
Mitochondria are the cell's power plant to satisfy the energy demands. However, dysfunctional mitochondria can cause overproduction of reactive oxygen species (ROS), oxidative stress, and alteration of calcium homeostasis, which are the hallmarks of mitochondrial diseases. Under prolong oxidative stress, repeated cytosolic calcium elevations even only transiently, can lead to activation of some enzymes. One calcium-activated enzyme with demonstrated pathophysiological important in mitochondrial disease is tissue transglutaminase (TG2)...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
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