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https://www.readbyqxmd.com/read/28822817/rosiglitazone-promotes-cardiac-hypertrophy-and-alters-chromatin-remodeling-in-isolated-cardiomyocytes
#1
Lama Fawaz Pharaon, Naglaa Fathi El-Orabi, Muhammad Kunhi, Nadya Al Yacoub, Salma Mahmoud Awad, Coralie Poizat
Rosiglitazone is an anti-diabetic agent that raised a major controversy over its cardiovascular adverse effects. There is in vivo evidence that Rosiglitazone promotes cardiac hypertrophy by PPAR -γ-independent mechanisms. However, whether Rosiglitazone directly alters hypertrophic growth in cardiac cells is unknown. Chromatin remodeling by histone post-translational modifications has emerged as critical for many cardiomyopathies. Based on these observations, this study was initiated to investigate the cardiac hypertrophic effect of Rosiglitazone in a cellular model of primary neonatal rat cardiomyocytes (NRCM)...
August 16, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28822219/regulation-of-protein-function-by-s-nitrosation-and-s-glutathionylation-processes-and-targets-in-cardiovascular-pathophysiology
#2
Eugenia Belcastro, Caroline Gaucher, Alessandro Corti, Pierre Leroy, Isabelle Lartaud, Alfonso Pompella
Decades of chemical, biochemical and pathophysiological research have established the relevance of post-translational protein modifications induced by processes related to oxidative stress, with critical reflections on cellular signal transduction pathways. A great deal of the socalled 'redox regulation' of cell function is in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific aminoacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues have received most attention, due to the critical roles they play in determining the structure/function correlates in proteins...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28821720/structural-basis-for-the-broad-substrate-specificity-of-the-human-tyrosylprotein-sulfotransferase-1
#3
Shinnosuke Tanaka, Toshiaki Nishiyori, Hidetaka Kojo, Reo Otsubo, Moe Tsuruta, Katsuhisa Kurogi, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara, Yoshimitsu Kakuta
Tyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyze post-translational tyrosine sulfation of proteins. In humans, there are only two TPST isoforms, designated TPST1 and TPST2. In a previous study, we reported the crystal structure of TPST2, which revealed the catalytic mechanism of the tyrosine sulfation reaction. However, detailed molecular mechanisms underlying how TPSTs catalyse a variety of substrate proteins with different efficiencies and how TPSTs catalyze the sulfation of multiple tyrosine residues in a substrate protein remain unresolved...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820317/ulk1-ubiquitylation-is-regulated-by-phosphorylation-on-its-carboxy-terminus
#4
Francesca Nazio, Marianna Carinci, Francesco Cecconi
Autophagy is a highly conserved process that acts sequestering cytoplasmic components for their degradation by the lysosomes. It consists of several sequential steps that have to be finely regulated to ensure both its progression and termination. Post-translational modifications (PTMs) play an important role in regulating ATG proteins function in different stages of autophagy. Recently, we demonstrated that, during prolonged starvation, ULK1 protein is specifically ubiquitylated by NEDD4L, and that this regulation is important to protect cells against excessive autophagy...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820289/recent-advances-in-quantitative-and-chemical-proteomics-for-autophagy-studies
#5
Yin-Kwan Wong, Jianbin Zhang, Zi-Chun Hua, Qingsong Lin, Han-Ming Shen, Jigang Wang
Macroautophagy/autophagy is an evolutionarily well-conserved cellular degradative process with important biological functions that is closely implicated in health and disease. In recent years, quantitative mass spectrometry-based proteomics and chemical proteomics have emerged as important tools for the study of autophagy, through large-scale unbiased analysis of the proteome or through highly specific and accurate analysis of individual proteins of interest. At present, a variety of approaches have been successfully applied, including (i) expression and interaction proteomics for the study of protein post-translational modifications, (ii) investigating spatio-temporal dynamics of protein synthesis and degradation, and (iii) direct determination of protein activity and profiling molecular targets in the autophagic process...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820267/causes-and-significance-of-increased-compound-potency-in-cellular-or-physiological-contexts
#6
Adam G Schwaid, Ivan Cornella-Taracido
Compound potency is a key metric that is often used to drive medicinal chemistry programs. Compound potency is also taken into account when identifying the mechanism of action of compounds whose pharmacological target is unknown, particularly when these compounds are identified in phenotypic screens. Often compound potency is determined from assays using recombinantly generated, purified protein. It is well understood in the medicinal chemistry community that potency measured with recombinant enzyme and potency measured in cell may not entirely coincide...
August 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28820257/residues-comprising-the-enhanced-aromatic-sequon-influence-protein-n-glycosylation-efficiency
#7
Yen-Wen Huang, Hwai-I Yang, Ying-Ta Wu, Tsui-Ling Hsu, Tzu-Wen Lin, Jeffery W Kelly, Chi-Huey Wong
N-glycosylation is an important co- and/or post-translational modification that occurs on the vast majority of the 1/3 of the mammalian proteome that traverses the cellular secretory pathway, regulating glycoprotein folding and functions. Previous studies on the sequence requirements for N-glycosylation have yielded the Asn-X-Ser/Thr (NXS/T) sequon and the enhanced aromatic sequons (Phe-X-Asn-X-Thr and Phe-X-X-Asn-X-Thr) which can be efficiently N-glycosylated. To further investigate the influence of sequence variation on N-glycosylation efficiency in the context of a 5-residue enhanced aromatic sequon, we used the human CD2 adhesion domain (hCD2ad) to screen the i-2, i-1, i+1 and i+2 residues flanking Asn at the i position...
August 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28820180/osteogenesis-imperfecta
#8
REVIEW
Joan C Marini, Antonella Forlino, Hans Peter Bächinger, Nick J Bishop, Peter H Byers, Anne De Paepe, Francois Fassier, Nadja Fratzl-Zelman, Kenneth M Kozloff, Deborah Krakow, Kathleen Montpetit, Oliver Semler
Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure...
August 18, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28820059/histone-modifications-in-aging%C3%AF-the-underlying-mechanisms-and-implications
#9
Yuan Wang, Quan Yuan, Liang Xie
Aging is characterized by time-dependent functional decline, which results in the reduced ability to cope with physiological challenges. The aging process can be affected by genetic factors, environment factors, epigenetic factors, and several stochastic factors. Epigenetic marker alteration during aging has been widely monitored and studied recently, since these epigenetic alterations are theoretically reversible. Histone post-translational modifications have been found to play a crucial role in epigenetic alteration during aging, among which histone methylation and histone acetylation are emerging as two well-documented modification methods...
August 17, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28819816/a-new-non-radioactive-deoxyhypusine-synthase-assay-adaptable-to-high-throughput-screening
#10
Myung Hee Park, Ajeet Mandal, Swati Mandal, Edith C Wolff
Deoxyhypusine synthase (DHS) catalyzes the post-translational modification of eukaryotic translation factor 5A (eIF5A) by the polyamine, spermidine, that converts one specific lysine residue to deoxyhypusine [N (ε) -4-aminobutyl(lysine)], which is subsequently hydroxylated to hypusine [N (ε) -4-amino-2-hydroxybutyl(lysine)]. Hypusine synthesis represents the most critical function of polyamine. As eIF5A has been implicated in various human diseases, identification of specific inhibitors of hypusine modification is of vital importance...
August 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28819043/increased-acetylation-of-microtubules-rescues-human-tau-induced-microtubule-defects-and-neuromuscular-junction-abnormalities-in-drosophila
#11
Chuan-Xi Mao, Xue Wen, Shan Jin, Yong Q Zhang
Tau normally associates with and stabilizes microtubules (MTs), but is hyperphosphorylated and aggregated into neurofibrillary tangles in Alzheimer's disease and related neurodegenerative diseases, which are collectively known as tauopathies. MTs are regulated by different forms of post-translational modification including acetylation; acetylated MTs represent a more stable microtubule population. In our previous study, we show that inhibition of histone deacetylase 6 (HDAC6), which deacetylates tubulin at lysine 40, rescues defects in MTs and in neuromuscular junction growth caused by tau overexpression...
August 17, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28816419/tubulin-acetylation-accompanies-autophagy-development-induced-by-different-abiotic-stimuli-in-arabidopsis-thaliana
#12
Vira Olenieva, Dmytro Lytvyn, Alla Yemets, Catherine Bergounioux, Yaroslav Blume
Microtubules (MTs) play an important role in the regulation of autophagy development in yeast and animal as well as in plant cells. MTs participate in maturation and traffic of autophagosomes through their dynamic state changes and post-translational modifications of tubulin, namely acetylation. We subjected Arabidopsis thaliana seedlings to metabolic-, salt-, osmotic stresses as well as irradiation of ultraviolet B and investigated the involvement of plant MTs in the development of stress-induced autophagy via tubulin acetylation...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28816396/identification-of-novel-site-specific-alterations-in-the-modification-level-of-myelin-basic-protein-isolated-from-mouse-brain-at-different-ages-using-capillary-electrophoresis-mass-spectrometry
#13
Bettina Sarg, Klaus Faserl, Herbert H Lindner
Myelin basic protein (MBP) is a multifunctional protein involved in maintaining the stability and integrity of the myelin sheath by a variety of interactions with membranes and other proteins. MBP is subjected to extensive post-translational modifications (PTMs) that are known to be crucial for the regulation of these interactions. Here we report capillary electrophoresis-mass spectrometric (CE-MS) analysis for the separation and identification of MBP peptides that incorporate the same PTM at different sites, creating multiple localization variants, and the ability to analyze challenging modifications such as asparagine and glutamine deamidation, isomerization and arginine citrullination...
August 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28816391/cytoskeleton-and-nucleoskeleton-involvement-in-processes-of-cytomixis-in-plants
#14
REVIEW
E A Kravets, A I Yemets, Ya B Blume
Cytomixis, is a form of cell-to-cell nuclear migration that involves the interaction of dynamic cytoskeletal components with the nucleus through signalling systems and linker complexes. In cytomixis two known mechanisms can be involved: actomyosin and/or microtubules and their associated motors. Perinuclear actin anchors and determines the direction of nuclear movement. In microsporogenesis cytomixis is probably initiated by a cascade of signals that trigger prophase reorganization of nucleus and cytoskeleton, and is a result of cytoskeletal protein activation, as well as a weakening of mechanisms responsible for anchoring the nucleus...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28814501/knockout-of-the-golgi-stacking-proteins-grasp55-and-grasp65-impairs-golgi-structure-and-function
#15
Michael E Bekier, Leibin Wang, Jie Li, Haoran Huang, Danming Tang, Xiaoyan Zhang, Yanzhuang Wang
GRASP65 and GRASP55 were originally identified as Golgi stacking proteins; however, subsequent GRASP knockdown experiments yielded inconsistent results with respect to the Golgi structure, indicating a limitation of RNAi-based depletion. In this study, we have applied the recently developed CRISPR-Cas9 technology to knock out GRASP55 and GRASP65, individually or in combination, in HeLa and HEK293 cells. We show that double knockout of GRASP proteins disperses the Golgi stack into single cisternae and tubulovesicular structures, accelerates protein trafficking, and impairs accurate glycosylation of proteins and lipids...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28813682/circadian-and-feeding-rhythms-orchestrate-the-diurnal-liver-acetylome
#16
Daniel Mauvoisin, Florian Atger, Loïc Dayon, Antonio Núñez Galindo, Jingkui Wang, Eva Martin, Laetitia Da Silva, Ivan Montoliu, Sebastiano Collino, Francois-Pierre Martin, Joanna Ratajczak, Carles Cantó, Martin Kussmann, Felix Naef, Frédéric Gachon
Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813517/prmepred-a-protein-arginine-methylation-prediction-tool
#17
Pawan Kumar, Joseph Joy, Ashutosh Pandey, Dinesh Gupta
Protein methylation is an important Post-Translational Modification (PTMs) of proteins. Arginine methylation carries out and regulates several important biological functions, including gene regulation and signal transduction. Experimental identification of arginine methylation site is a daunting task as it is costly as well as time and labour intensive. Hence reliable prediction tools play an important task in rapid screening and identification of possible methylation sites in proteomes. Our preliminary assessment using the available prediction methods on collected data yielded unimpressive results...
2017: PloS One
https://www.readbyqxmd.com/read/28812749/radical-driven-processes-within-a-peptidic-sequence-of-type-i-collagen-upon-single-photon-ionisation-in-the-gas-phase
#18
Lucas Schwob, Mathieu Lalande, Dmitrii Egorov, Jimmy Rangama, Ronnie Hoekstra, Violaine Vizcaino, Thomas Schlathölter, Jean-Christophe Poully
We report on an experimental single-photon absorption study on gas-phase protonated collagen peptides employing a combination of mass spectrometry and synchrotron radiation. Partial ion yields for the main photoabsorption products vary steadily with photon energy over the range from 14 to 545 eV. At low energy, non-dissociative photoionisation competes with neutral molecule loss from the precursor ion, whereas fragmentation of the peptide backbone dominates at soft X-ray energies. Neutral molecule losses from the ionised peptide are found to have low energy barriers and most likely involve amino-acid residue side-chains with radical character, in particular aspartic acid...
August 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28812241/plasma-glycoproteomic-study-of-therapeutic-hypothermia-reveals-novel-markers-predicting-neurologic-outcome-post-cardiac-arrest
#19
Wenjun Deng, Jing Cao, Lei Chen, David McMullin, James L Januzzi, Ferdinando S Buonanno, Eng H Lo, MingMing Ning
Therapeutic hypothermia (TH) is a neuroprotective treatment post-cardiac arrest but is grossly underutilized. After TH induction, traditional biomarkers and parameters can no long predict clinical outcome due to a lack of understanding of hypothermic response. Innovative approaches to better understand the clinical effect of TH will help to prognosticate outcome and expand beneficial population. Protein glycosylation is an important extracellular post-translational modification, regulating various extracellular signaling pathways...
August 15, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28810660/recent-advancements-in-understanding-mammalian-o-mannosylation
#20
M Osman Sheikh, Stephanie M Halmo, Lance Wells
The post-translational glycosylation of select proteins by O-linked mannose (O-mannose or O-man) is a conserved modification from yeast to humans and has been shown to be necessary for proper development and growth. The most well studied O-mannosylated mammalian protein is α-dystroglycan (α-DG). Hypoglycosylation of α-DG results in varying severities of congenital muscular dystrophies, cancer progression and metastasis, and inhibited entry and infection of certain arenaviruses. Defects in the gene products responsible for post-translational modification of α-DG, primarily glycosyltransferases, are the basis for these diseases...
September 1, 2017: Glycobiology
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