scholarly journals Quantitative Temporal Analysis of Protein Dynamics in Maladaptive Cardiac Remodeling

2018 ◽  
Author(s):  
Daniel B. McClatchy ◽  
Yuanhui Ma ◽  
David A. Liem ◽  
Dominic C.M. Ng ◽  
Peipei Ping ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Protein Turnover ◽  
Heart Diseases ◽  
Temporal Analysis ◽  
Complex Nature ◽  
The Novel ◽  
Turnover Rates ◽  
Biochemical Mechanisms ◽  
And Oxidative Stress ◽  
Synthesis And Degradation

AbstractMaladaptive cardiac remodeling (MCR) is a complex dynamic process common to many heart diseases. MCR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of MCR, but greater insight into the processes and mechanisms has the potential to identify new therapeutic targets. To provide a deeper understanding of this important cardiac process, we applied a new proteomic technique, PALM (Pulse Azidohomoalanine in Mammals), to quantitate the newly-synthesized protein (NSP) changes during the progression of isoproterenol (ISO)-induced MCR in the mouse left ventricle. This analysis revealed a complex combination of adaptive and maladaptive alterations at acute and prolonged time points including the identification of proteins not previously associated with MCR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying MCR. The novel integration of analyzing NSPs together with their protein turnover rates demonstrated that alterations in specific biological pathways (e.g., inflammation and oxidative stress) are produced by differential regulation of protein synthesis and degradation.

scholarly journals Proteome dynamics during homeostatic scaling in cultured neurons

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aline Ricarda Dörrbaum ◽  
Beatriz Alvarez-Castelao ◽  
Belquis Nassim-Assir ◽  
Julian D Langer ◽  
Erin M Schuman
Keyword(s):  
Protein Synthesis ◽  
Protein Function ◽  
Protein Turnover ◽  
Experimental Approach ◽  
Large Fraction ◽  
Synaptic Proteins ◽  
Turnover Rates ◽  
Cellular Environment ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Protein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, and by the cellular environment (Dörrbaum et al., 2018). Here, we advanced our experimental approach to quantify changes in protein synthesis and degradation, as well as the resulting changes in protein turnover or abundance in rat primary hippocampal cultures during homeostatic scaling. Our data demonstrate that a large fraction of the neuronal proteome shows changes in protein synthesis and/or degradation during homeostatic up- and down-scaling. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.

scholarly journals Slowed Protein Turnover in Aging Drosophila Reflects a Shift in Cellular Priorities

2021 ◽  
Author(s):  
Evelyn S Vincow ◽  
Ruth E Thomas ◽  
Gennifer E Merrihew ◽  
Michael J MacCoss ◽  
Leo J Pallanck
Keyword(s):  
Quality Control ◽  
Protein Turnover ◽  
Protein Quality ◽  
Fruit Fly ◽  
Turnover Rates ◽  
High Turnover ◽  
Age Related ◽  
System Collapse ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Abstract The accumulation of protein aggregates and dysfunctional organelles as organisms age has led to the hypothesis that aging involves general breakdown of protein quality control. We tested this hypothesis using a proteomic and informatic approach in the fruit fly Drosophila melanogaster. Turnover of most proteins was markedly slower in old flies. However, ribosomal and proteasomal proteins maintained high turnover rates, suggesting that the observed slowdowns in protein turnover might not be due to a global failure of quality control. As protein turnover reflects the balance of protein synthesis and degradation, we investigated whether decreases in synthesis or decreases in degradation would best explain the observed slowdowns in protein turnover. We found that while many individual proteins in old flies showed slower turnover due to decreased degradation, an approximately equal number showed slower turnover due to decreased synthesis, and enrichment analyses revealed that translation machinery itself was less abundant. Mitochondrial complex I subunits and glycolytic enzymes were decreased in abundance as well, and proteins involved in glutamine-dependent anaplerosis were increased, suggesting that old flies modify energy production to limit oxidative damage. Together, our findings suggest that age-related proteostasis changes in Drosophila represent a coordinated adaptation rather than a system collapse.

scholarly journals An atlas of protein turnover rates in mouse tissues

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zach Rolfs ◽  
Brian L. Frey ◽  
Xudong Shi ◽  
Yoshitaka Kawai ◽  
Lloyd M. Smith ◽  
...  
Keyword(s):  
Protein Turnover ◽  
Isotope Labeling ◽  
Turnover Rates ◽  
Visualization Software ◽  
Degradation Rates ◽  
Mouse Tissues ◽  
Related Drug ◽  
Synthesis And Degradation ◽  
Mammalian Protein

AbstractProtein turnover is critical to cellular physiology as well as to the growth and maintenance of tissues. The unique synthesis and degradation rates of each protein help to define tissue phenotype, and knowledge of tissue- and protein-specific half-lives is directly relevant to protein-related drug development as well as the administration of medical therapies. Using stable isotope labeling and mass spectrometry, we determine the in vivo turnover rates of thousands of proteins—including those of the extracellular matrix—in a set of biologically important mouse tissues. We additionally develop a data visualization platform, named ApplE Turnover, that enables facile searching for any protein of interest in a tissue of interest and then displays its half-life, confidence interval, and supporting measurements. This extensive dataset and the corresponding visualization software provide a reference to guide future studies of mammalian protein turnover in response to physiologic perturbation, disease, or therapeutic intervention.

scholarly journals Proteome turnover in the bloodstream and procyclic forms of Trypanosoma brucei measured by quantitative proteomics

2019 ◽  
Vol 4 ◽  
pp. 152 ◽  
Author(s):  
Michele Tinti ◽  
Maria Lucia S. Güther ◽  
Thomas W. M. Crozier ◽  
Angus I. Lamond ◽  
Michael A. J. Ferguson
Keyword(s):  
Trypanosoma Brucei ◽  
Protein Turnover ◽  
Cellular Localization ◽  
Enzyme Inhibitors ◽  
Mass Spectrometry Analysis ◽  
Turnover Rates ◽  
Stable Isotope Labelling ◽  
Spectrometry Analysis ◽  
Web Resource ◽  
Synthesis And Degradation

Background: Cellular proteins vary significantly in both abundance and turnover rates. These parameters depend upon their rates of synthesis and degradation and it is useful to have access to data on protein turnover rates when, for example, designing genetic knock-down experiments or assessing the potential usefulness of covalent enzyme inhibitors. Little is known about the nature and regulation of protein turnover in Trypanosoma brucei, the etiological agent of human and animal African trypanosomiasis. Methods: To establish baseline data on T. brucei proteome turnover, a Stable Isotope Labelling with Amino acids in Cell culture (SILAC)-based mass spectrometry analysis was performed to reveal the synthesis and degradation profiles for thousands of proteins in the bloodstream and procyclic forms of this parasite. Results: This analysis revealed a slower average turnover rate of the procyclic form proteome relative to the bloodstream proteome. As expected, many of the proteins with the fastest turnover rates have functions in the cell cycle and in the regulation of cytokinesis in both bloodstream and procyclic forms. Moreover, the cellular localization of T. brucei proteins correlates with their turnover, with mitochondrial and glycosomal proteins exhibiting slower than average turnover rates. Conclusions: The intention of this study is to provide the trypanosome research community with a resource for protein turnover data for any protein or group of proteins. To this end, bioinformatic analyses of these data are made available via an open-access web resource with data visualization functions.

scholarly journals Protein turnover is elevated in muscle of mdx mice in vivo

1990 ◽  
Vol 268 (3) ◽  
pp. 795-797 ◽  
Author(s):  
P A MacLennan ◽  
R H T Edwards
Keyword(s):  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mdx Mice ◽  
Turnover Rates ◽  
Wild Type ◽  
Dystrophin Deficiency ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

mdx mice lack the protein dystrophin, the absence of which causes Duchenne muscular dystrophy in humans. To examine how mdx mice maintain muscle mass despite dystrophin deficiency, we measured protein turnover rates in muscles of mdx and wild-type (C57BL/10) mice in vivo. At all ages studied, rates of muscle protein synthesis and degradation were higher in mdx than in C57BL/10 mice.

Association and treatment of diabetes in patients affected by Covid-19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1198-1201
Author(s):  
Syed Yasir Afaque
Keyword(s):  
Diabetes Mellitus ◽  
Prognostic Value ◽  
Heart Diseases ◽  
The Novel ◽  
The World ◽  
Treatment Of Diabetes ◽  
Coronavirus Infection ◽  
Composite Outcomes ◽  
Novel Coronavirus ◽  
The Impact

In December 2019, a unique coronavirus infection, SARS-CoV-2, was first identified in the province of Wuhan in China. Since then, it spread rapidly all over the world and has been responsible for a large number of morbidity and mortality among humans. According to a latest study, Diabetes mellitus, heart diseases, Hypertension etc. are being considered important risk factors for the development of this infection and is also associated with unfavorable outcomes in these patients. There is little evidence concerning the trail back of these patients possibly because of a small number of participants and people who experienced primary composite outcomes (such as admission in the ICU, usage of machine-driven ventilation or even fatality of these patients). Until now, there are no academic findings that have proven independent prognostic value of diabetes on death in the novel Coronavirus patients. However, there are several conjectures linking Diabetes with the impact as well as progression of COVID-19 in these patients. The aim of this review is to acknowledge about the association amongst Diabetes and the novel Coronavirus and the result of the infection in such patients.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

scholarly journals Nuclear cGAS: sequestration and beyond

2021 ◽  
Author(s):  
Juli Bai ◽  
Feng Liu
Keyword(s):  
Innate Immune ◽  
Complex Nature ◽  
Type I ◽  
Replication Forks ◽  
The Novel ◽  
Nuclear Function ◽  
Double Stranded Dna ◽  
Open Questions ◽  
Established Role ◽  
Dependent Signaling Pathway

AbstractThe cyclic GMP-AMP (cGAMP) synthase (cGAS) has been identified as a cytosolic double stranded DNA sensor that plays a pivotal role in the type I interferon and inflammation responses via the STING-dependent signaling pathway. In the past several years, a growing body of evidence has revealed that cGAS is also localized in the nucleus where it is associated with distinct nuclear substructures such as nucleosomes, DNA replication forks, the double-stranded breaks, and centromeres, suggesting that cGAS may have other functions in addition to its role in DNA sensing. However, while the innate immune function of cGAS is well established, the non-canonical nuclear function of cGAS remains poorly understood. Here, we review our current understanding of the complex nature of nuclear cGAS and point to open questions on the novel roles and the mechanisms of action of this protein as a key regulator of cell nuclear function, beyond its well-established role in dsDNA sensing and innate immune response.

scholarly journals Influence of Subcellular Localization and Functional State on Protein Turnover

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1747
Author(s):  
Roya Yousefi ◽  
Kristina Jevdokimenko ◽  
Verena Kluever ◽  
David Pacheu-Grau ◽  
Eugenio F. Fornasiero
Keyword(s):  
Subcellular Localization ◽  
Functional State ◽  
Protein Turnover ◽  
Protein Localization ◽  
Small Gtpase ◽  
Turnover Rates ◽  
Cellular Behavior ◽  
Two Factors ◽  
Brain Creatine Kinase ◽  
Selection Of

Protein homeostasis is an equilibrium of paramount importance that maintains cellular performance by preserving an efficient proteome. This equilibrium avoids the accumulation of potentially toxic proteins, which could lead to cellular stress and death. While the regulators of proteostasis are the machineries controlling protein production, folding and degradation, several other factors can influence this process. Here, we have considered two factors influencing protein turnover: the subcellular localization of a protein and its functional state. For this purpose, we used an imaging approach based on the pulse-labeling of 17 representative SNAP-tag constructs for measuring protein lifetimes. With this approach, we obtained precise measurements of protein turnover rates in several subcellular compartments. We also tested a selection of mutants modulating the function of three extensively studied proteins, the Ca2+ sensor calmodulin, the small GTPase Rab5a and the brain creatine kinase (CKB). Finally, we followed up on the increased lifetime observed for the constitutively active Rab5a (Q79L), and we found that its stabilization correlates with enlarged endosomes and increased interaction with membranes. Overall, our data reveal that both changes in protein localization and functional state are key modulators of protein turnover, and protein lifetime fluctuations can be considered to infer changes in cellular behavior.

Sign in / Sign up

Export Citation Format

Share Document