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Protein turnover

Paul A Gurbel, Kevin P Bliden, Rahul Chaudhary, Jeff Patrick, Fang Liu, Gailing Chen, Christopher McLeod, Udaya S Tantry
High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162...
September 20, 2016: American Journal of Cardiology
Zhen Wang, Eric P Chang, Vern L Schramm
Transition path sampling simulations have proposed that human heart lactate dehydrogenase (LDH) employs protein promoting vibrations (PPVs) on the femtosecond (fs) to picosecond (ps) timescale to promote crossing of the chemical barrier. This chemical barrier involves both hydride and proton transfers to pyruvate to form L-lactate, using reduced nicotinamide adenine dinucleotide (NADH) as the cofactor. Here we report experimental evidence from three types of isotope effect experiments that support coupling of the promoting vibrations to barrier crossing and the coincidence of hydride and proton transfer...
October 21, 2016: Journal of the American Chemical Society
Yaohong Wang, Sudeep P George, Swati Roy, Eric Pham, Amin Esmaeilniakooshkghazi, Seema Khurana
In the small intestine, epithelial cells are derived from stem cells in the crypts, migrate up the villus as they differentiate and are ultimately shed from the villus tips. This process of proliferation and shedding is tightly regulated to maintain the intestinal architecture and tissue homeostasis. Apoptosis regulates both the number of stem cells in the crypts as well as the sloughing of cells from the villus tips. Previously, we have shown that villin, an epithelial cell-specific actin-binding protein functions as an anti-apoptotic protein in the gastrointestinal epithelium...
October 21, 2016: Scientific Reports
Hisato Kawakami, Shengbing Huang, Krishnendu Pal, Shamit K Dutta, Debabrata Mukhopadhyay, Frank A Sinicrope
Oncogenic BRAFV600E mutations activate MAP kinase signaling and are associated with treatment resistance and poor prognosis in patients with colorectal cancer (CRC). In BRAFV600E mutant CRCs, treatment failure may be related to BRAFV600E -mediated apoptosis resistance that occurs by an as yet undefined mechanism. We found that BRAFV600E can upregulate anti-apoptotic MCL-1 in a gene dose-dependent manner using CRC cell lines isogenic for BRAF. BRAFV600E -induced MCL-1 upregulation was confirmed by ectopic BRAFV600E expression that activated MEK/ERK signaling to phosphorylate (MCL-1Thr163) and stabilize MCL-1...
October 7, 2016: Molecular Cancer Therapeutics
Kevin A Welle, Tian Zhang, Jennifer R Hyrohorenko, Shichen Shen, Jun Qu, Sina Ghaemmaghami
Recent advances in mass spectrometry have enabled system-wide analyses of protein turnover. By globally quantifying the kinetics of protein clearance and synthesis, these methodologies can provide important insights into the regulation of the proteome under varying cellular and environmental conditions. To facilitate such analyses, we have employed a methodology that combines metabolic isotopic labeling (Stable Isotope Labeling in Cell Culture - SILAC) with isobaric tagging (Tandem Mass Tags - TMT) for analysis of multiplexed samples...
October 20, 2016: Molecular & Cellular Proteomics: MCP
Christoph W Turck, Christian Webhofer, Markus Nussbaumer, Larysa Teplytska, Alon Chen, Giuseppina Maccarrone, Michaela D Filiou
PURPOSE: In this work we discuss how in vivo (15) N metabolic labeling in combination with mass spectrometry simultaneously provides information on protein expression and protein turnover. EXPERIMENTAL DESIGN: We metabolically labeled mice with the stable nitrogen isotope (15) N using a (15) N-enriched diet and analyzed (15) N-labeled vs. unlabeled ((14) N) brain tissue with LC-MS/MS. We then compared the (14) N vs.(15) N peptide isotopologue clusters of (14) N and (15) N-labeled Dihydropyrimidinase-related (DPYSL) proteins...
October 20, 2016: Proteomics. Clinical Applications
Xiaoli Wang, Xiaofeng Cai, Chenxi Xu, Quanhua Wang, Shaojun Dai
Plant drought tolerance is a complex trait that requires a global view to understand its underlying mechanism. The proteomic aspects of plant drought response have been extensively investigated in model plants, crops and wood plants. In this review, we summarize recent proteomic studies on drought response in leaves to reveal the common and specialized drought-responsive mechanisms in different plants. Although drought-responsive proteins exhibit various patterns depending on plant species, genotypes and stress intensity, proteomic analyses show that dominant changes occurred in sensing and signal transduction, reactive oxygen species scavenging, osmotic regulation, gene expression, protein synthesis/turnover, cell structure modulation, as well as carbohydrate and energy metabolism...
October 18, 2016: International Journal of Molecular Sciences
Simona Citro, Susanna Chiocca
Attachment of ubiquitin or ubiquitin-like (Ubl) modifiers, such as the small ubiquitin-related modifier SUMO, is a posttranslational modification (PTM) that reversibly regulates the function and the stability of target proteins. The SUMO paralogs SUMO1 and SUMO2/3, although sharing a common conjugation pathway, seem to play different roles in the cell. Many regulatory mechanisms, which contribute to SUMO-paralog-specific modification, have emerged. We have recently found that cell environment affects SUMO-paralog-specific sumoylation of HDAC1, whose conjugation to SUMO1 and not to SUMO2 facilitates its protein turnover...
2017: Methods in Molecular Biology
Sharon L I Wong, Maria B Sukkar
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein which regulates interactions between cells and their surrounding extracellular matrix (ECM), and thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover. Studies in SPARC-null mice have revealed a critical role for SPARC in tissue development, injury and repair, and in the regulation of the immune response...
October 19, 2016: British Journal of Pharmacology
Xiang Yu, Matthew R Willmann, Stephen J Anderson, Brian D Gregory
RNA turnover is necessary for controlling proper mRNA levels post-transcriptionally. In general, RNA degradation is via exoribonucleases that degrade RNA either from the 5' end to the 3' end, such as XRN4, or in the opposite direction by the multi-subunit exosome complex. Here, we use genome-wide mapping of uncapped and cleaved transcripts to reveal the global landscape of co-translational mRNA decay in the Arabidopsis thaliana transcriptome. We found that this process leaves a clear three nucleotide periodicity in open reading frames...
October 7, 2016: Plant Cell
Victoria C Foletta, Michelle Palmieri, Joachim Kloehn, Shaun Mason, Stephen F Previs, Malcolm J McConville, Oliver M Sieber, Clinton R Bruce, Greg M Kowalski
Deuterated water (²H₂O), a stable isotopic tracer, provides a convenient and reliable way to label multiple cellular biomass components (macromolecules), thus permitting the calculation of their synthesis rates. Here, we have combined ²H₂O labelling, GC-MS analysis and a novel cell fractionation method to extract multiple biomass components (DNA, protein and lipids) from the one biological sample, thus permitting the simultaneous measurement of DNA (cell proliferation), protein and lipid synthesis rates...
October 13, 2016: Metabolites
Bagher Larijani, Arash Hossein-Nezhad, Elham Feizabad, Zhila Maghbooli, Hossein Adibi, Majid Ramezani, Eghbal Taheri
BACKGROUND: This cross-sectional population-based study was conducted to elucidate the prevalence of vitamin D deficiency, bone turnover marker's variation and its influencing factors among adolescents of Tehran. METHODS: Totally 444 middle and high school (53.6 % in high school) students (both girls and boys) were recruited. A short food frequency questionnaire designed to estimate dietary calcium and vitamin D consumption. Serum levels of calcium, phosphorus, parathyroid hormone (PTH), bone specific alkaline phosphates, 25 (OH) vitamin D, osteocalcin, cross-linked C-telopeptide (CTX), total protein, albumin and creatinine were determined...
2016: Journal of Diabetes and Metabolic Disorders
Fiorenza Fumagalli, Julia Noack, Timothy J Bergmann, Eduardo Cebollero Presmanes, Giorgia Brambilla Pisoni, Elisa Fasana, Ilaria Fregno, Carmela Galli, Marisa Loi, Tatiana Soldà, Rocco D'Antuono, Andrea Raimondi, Martin Jung, Armin Melnyk, Stefan Schorr, Anne Schreiber, Luca Simonelli, Luca Varani, Caroline Wilson-Zbinden, Oliver Zerbe, Kay Hofmann, Matthias Peter, Manfredo Quadroni, Richard Zimmermann, Maurizio Molinari
The endoplasmic reticulum (ER) is a site of protein biogenesis in eukaryotic cells. Perturbing ER homeostasis activates stress programs collectively called the unfolded protein response (UPR). The UPR enhances production of ER-resident chaperones and enzymes to reduce the burden of misfolded proteins. On resolution of ER stress, ill-defined, selective autophagic programs remove excess ER components. Here we identify Sec62, a constituent of the translocon complex regulating protein import in the mammalian ER, as an ER-resident autophagy receptor...
October 17, 2016: Nature Cell Biology
Débora Broch Trentini, Marcin Józef Suskiewicz, Alexander Heuck, Robert Kurzbauer, Luiza Deszcz, Karl Mechtler, Tim Clausen
Protein turnover is a tightly controlled process critical for the removal of aberrant polypeptides and for cellular signalling. Whereas ubiquitin marks eukaryotic proteins for proteasomal degradation, a general tagging system for the equivalent bacterial Clp proteases is not known. Here we address the targeting mechanism of the ClpC:ClpP proteolytic complex from Bacillus subtilis. Quantitative affinity proteomics using a ClpP trapping mutant show that proteins phosphorylated on arginine residues are selectively targeted to ClpC:ClpP...
October 6, 2016: Nature
Masakazu Sugiyama, Tomoharu Yoshizumi, Yoshihiro Yoshida, Yuki Bekki, Yoshihiro Matsumoto, Shohei Yoshiya, Takeo Toshima, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Shinji Okano, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara
Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62 and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically-induced liver injury...
October 17, 2016: Journal of Cellular Physiology
Peng Zou, Longhua Liu, Louise D Zheng, Kyle K Payne, Masoud H Manjili, Michael O Idowu, Jinfeng Zhang, Eva M Schmelz, Zhiyong Cheng
Overactive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1), was accompanied with increased mitochondrial biogenesis markers (PGC1α, NRF1, and Tfam) in breast cancer cells. However, mitochondrial number was reduced, which was associated with lower mitochondrial oxidative capacity in breast cancer cells...
2016: Oxidative Medicine and Cellular Longevity
Haolin Chen, Yiyan Wang, Renshan Ge, Barry R Zirkin
Adult Leydig cells develop from undifferentiated mesenchymal-like stem cells (stem Leydig cells, SLCs) present in the interstitial compartment of the early postnatal testis. Putative SLCs also have been identified in peritubular and perivascular locations of the adult testis. The latter cells, which normally are quiescent, are capable of regenerating new Leydig cells upon the loss of the adult cells. Recent studies have identified several protein markers to identify these cells, including nestin, PDGFRα, COUP-TFII, CD51 and CD90...
October 12, 2016: Molecular and Cellular Endocrinology
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
Chris McGlory, Michaela C Devries, Stuart M Phillips
Exercise results in the rapid remodelling of skeletal muscle imparting a positive impact on human health. This process is underpinned by acute and chronic changes in both gene and protein synthesis. In this short review we provide a brief summary of our current understanding regarding how exercise influences these processes as well as the subsequent impact on muscle protein turnover and resultant shift in muscle phenotype. We explore concepts of ribosomal biogenesis and the potential role of increased translational capacity versus translational efficiency in contributing to muscular hypertrophy...
October 14, 2016: Journal of Applied Physiology
Khoa Nguyen, Michael Vaughn, Paul Frymier, Barry D Bruce
The reduction rate of photo-oxidized Photosystem I (PSI) with various natural and artificial electron donors have been well studied by transient absorption spectroscopy. The electron transfer rate from various donors to P700(+) has been measured for a wide range of photosynthetic organisms encompassing cyanobacteria, algae, and plants. PSI can be a limiting component due to tedious extraction and purification methods required for this membrane protein. In this report, we have determined the in vivo, intracellular cytochrome c 6 (cyt c 6)/PSI ratio in Thermosynechococcus elongatus (T...
October 13, 2016: Photosynthesis Research
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