scholarly journals Hydrogen Indirectly Suppresses Increases in Hydrogen Peroxide in Cytoplasmic Hydroxyl Radical-Induced Cells and Suppresses Cellular Senescence

2019 ◽  
Vol 20 (2) ◽  
pp. 456 ◽  
Author(s):  
Takahiro Sakai ◽  
Ryosuke Kurokawa ◽  
Shin-ichi Hirano ◽  
Jun Imai
Keyword(s):  
Hydrogen Peroxide ◽  
Hydroxyl Radical ◽  
Cellular Senescence ◽  
Physiological Role ◽  
Lipid Peroxide ◽  
Gut Bacteria ◽  
The Body ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Plant Fibers

Bacteria inhabiting the human gut metabolize microbiota-accessible carbohydrates (MAC) contained in plant fibers and subsequently release metabolic products. Gut bacteria produce hydrogen (H2), which scavenges the hydroxyl radical (•OH). Because H2 diffuses within the cell, it is hypothesized that H2 scavenges cytoplasmic •OH (cyto •OH) and suppresses cellular senescence. However, the mechanisms of cyto •OH-induced cellular senescence and the physiological role of gut bacteria-secreted H2 have not been elucidated. Based on the pyocyanin-stimulated cyto •OH-induced cellular senescence model, the mechanism by which cyto •OH causes cellular senescence was investigated by adding a supersaturated concentration of H2 into the cell culture medium. Cyto •OH-generated lipid peroxide caused glutathione (GSH) and heme shortage, increased hydrogen peroxide (H2O2), and induced cellular senescence via the phosphorylation of ataxia telangiectasia mutated kinase serine 1981 (p-ATMser1981)/p53 serine 15 (p-p53ser15)/p21 and phosphorylation of heme-regulated inhibitor (p-HRI)/phospho-eukaryotic translation initiation factor 2 subunit alpha serine 51 (p-eIF2α)/activating transcription factor 4 (ATF4)/p16 pathways. Further, H2 suppressed increased H2O2 by suppressing cyto •OH-mediated lipid peroxide formation and cellular senescence induction via two pathways. H2 produced by gut bacteria diffuses throughout the body to scavenge cyto •OH in cells. Therefore, it is highly likely that gut bacteria-produced H2 is involved in intracellular maintenance of the redox state, thereby suppressing cellular senescence and individual aging. Hence, H2 produced by intestinal bacteria may be involved in the suppression of aging.

scholarly journals rRNA Suppressor of a Eukaryotic Translation Initiation Factor 5B/Initiation Factor 2 Mutant Reveals a Binding Site for Translational GTPases on the Small Ribosomal Subunit

2008 ◽  
Vol 29 (3) ◽  
pp. 808-821 ◽  
Author(s):  
Byung-Sik Shin ◽  
Joo-Ran Kim ◽  
Michael G. Acker ◽  
Kathryn N. Maher ◽  
Jon R. Lorsch ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Ribosomal Subunit ◽  
The Body ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Small Ribosomal Subunit ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Initiation Factor 2 ◽  
Eukaryotic Translation Initiation

ABSTRACT The translational GTPases promote initiation, elongation, and termination of protein synthesis by interacting with the ribosome. Mutations that impair GTP hydrolysis by eukaryotic translation initiation factor 5B/initiation factor 2 (eIF5B/IF2) impair yeast cell growth due to failure to dissociate from the ribosome following subunit joining. A mutation in helix h5 of the 18S rRNA in the 40S ribosomal subunit and intragenic mutations in domain II of eIF5B suppress the toxic effects associated with expression of the eIF5B-H480I GTPase-deficient mutant in yeast by lowering the ribosome binding affinity of eIF5B. Hydroxyl radical mapping experiments reveal that the domain II suppressors interface with the body of the 40S subunit in the vicinity of helix h5. As the helix h5 mutation also impairs elongation factor function, the rRNA and eIF5B suppressor mutations provide in vivo evidence supporting a functionally important docking of domain II of the translational GTPases on the body of the small ribosomal subunit.

Impact of polychlorinated biphenyl Aroclor 1254 on testicular antioxidant system in adult rats

2005 ◽  
Vol 24 (2) ◽  
pp. 61-66 ◽  
Author(s):  
P Murugesan ◽  
J Senthilkumar ◽  
K Balasubramanian ◽  
M M Aruldhas ◽  
J Arunakaran
Keyword(s):  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Hydroxyl Radical ◽  
Polychlorinated Biphenyl ◽  
The Body ◽  
Male Rats ◽  
Ventral Prostate ◽  
Enzymatic Antioxidants ◽  
Aroclor 1254 ◽  
Adult Rats

To clarify the reproductive toxicity of polychlorinated biphenyl compounds through determination of testicular lipid peroxidation, reactive oxygen species and enzymatic and non-enzymatic antioxidants in rats exposed to Aroclor 1254. Adult male rats were administered Aroclor 1254 at a dose of 2 mg/kg per day ip for 30 days. The rats were sacrificed 24 hours after last dosing and the serum and other tissues collected and processed for relevant determinations. The body weight and the weights of the testis, epididymis, ventral prostate and seminal vesicle and the serum testosterone and estradiol were significantly decreased in Aroclor 1254 treated rats. The testicular lipid peroxidation, hydrogen peroxide and hydroxyl radical were significantly elevated whereas, testicular antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) were significantly decreased. The non-enzymatic antioxidants, vitamin C and vitamin E, were also decreased. These results suggest that Aroclor 1254 induces an increase in the lipid peroxidation, hydrogen peroxide and hydroxyl radical and diminish in the antioxidant defense system in rats, indicating that the free radical-dependent mechanism may play an important role in the testicular toxicity of polychlorinated biphenyls.

scholarly journals AMP-activated Protein Kinase Up-regulates Mitogen-activated Protein (MAP) Kinase-interacting Serine/Threonine Kinase 1a-dependent Phosphorylation of Eukaryotic Translation Initiation Factor 4E

2016 ◽  
Vol 291 (33) ◽  
pp. 17020-17027 ◽  
Author(s):  
Xiaoqing Zhu ◽  
Vivian Dahlmans ◽  
Ramon Thali ◽  
Christian Preisinger ◽  
Benoit Viollet ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Physiological Role ◽  
Cellular Systems ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is a molecular energy sensor that acts to sustain cellular energy balance. Although AMPK is implicated in the regulation of a multitude of ATP-dependent cellular processes, exactly how these processes are controlled by AMPK as well as the identity of AMPK targets and pathways continues to evolve. Here we identify MAP kinase-interacting serine/threonine protein kinase 1a (MNK1a) as a novel AMPK target. Specifically, we show AMPK-dependent Ser353 phosphorylation of the human MNK1a isoform in cell-free and cellular systems. We show that AMPK and MNK1a physically interact and that in vivo MNK1a-Ser353 phosphorylation requires T-loop phosphorylation, in good agreement with a recently proposed structural regulatory model of MNK1a. Our data suggest a physiological role for MNK1a-Ser353 phosphorylation in regulation of the MNK1a kinase, which correlates with increased eIF4E phosphorylation in vitro and in vivo.

scholarly journals Selenoproteins

2015 ◽  
Vol 69 (1-2) ◽  
pp. 75-89
Author(s):  
Svetlana Milanovic ◽  
Ivan Jovanovic ◽  
Olivera Valcic
Keyword(s):  
Hydrogen Peroxide ◽  
Trace Elements ◽  
Amino Acid ◽  
Integral Functional ◽  
Physiological Role ◽  
The Body ◽  
Essential Trace Element ◽  
Iodothyronine Deiodinases ◽  
Organic Hydroperoxides ◽  
Functional Part

Selenium is an essential trace element with multi significant role in the body. In contrast to other trace elements that appear as cofactors of certain enzymes, its physiological role is directly related to functions of proteins in composition of which it is cotranslationally installed by atypical amino acid selenocysteine. The group of proteins, in which composition selenocysteine is an integral functional part of polypeptides, are referred to as selenoproteins. The first enzyme that has been proven to have selenocysteine incorporated in its composition, is glutathione peroxidase (GPx). So far there have been identified 5 isoenzyme forms of GPx which reduce hydrogen peroxide and organic hydroperoxides, protecting cells from oxidative damage. Iodothyronine deiodinases (ID) are among the most important selenopoteins, being responsible for both activation and deactivation of thyroid hormones. So far there have been found over twenty selenoproteins, but only for some of them a physiological role is known.

scholarly journals Suurstoftoksisiteit

1990 ◽  
Vol 9 (3) ◽  
pp. 118-123
Author(s):  
C. A. Van der Westhuizen ◽  
M. Viljoen ◽  
M. J. Pitout ◽  
P. H. Van Papendorp
Keyword(s):  
Hydrogen Peroxide ◽  
Endoplasmic Reticulum ◽  
Hydroxyl Radical ◽  
Singlet Oxygen ◽  
Superoxide Anion ◽  
Energy Production ◽  
Plasma Membranes ◽  
The Body ◽  
Toxic Metabolites ◽  
Oxygen Metabolites

Oxygen has been discovered about 200 years ago. Since then the vital physiological involvement of oxygen in various biologi­cal processes, mainly energy production, has been established. However, in the body molecular oxygen can be converted to toxic oxygen metabolites such as superoxide anion, hydrogen peroxide, the hydroxyl radical and singlet oxygen. These toxic metabolites are produced mainly in the mitochondria, plasma membranes and endoplasmic reticulum.

scholarly journals The Universally Conserved ATPase YchF Regulates Translation of Leaderless mRNA in Response to Stress Conditions

2021 ◽  
Vol 8 ◽  
Author(s):  
Victoria Landwehr ◽  
Martin Milanov ◽  
Larissa Angebauer ◽  
Jiang Hong ◽  
Gabriela Jüngert ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Intracellular Transport ◽  
Ribosomal Subunit ◽  
Physiological Role ◽  
Mrna Translation ◽  
Stress Conditions ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Leaderless Mrna

The universally conserved P-loop GTPases control diverse cellular processes, like signal transduction, ribosome assembly, cell motility, and intracellular transport and translation. YchF belongs to the Obg-family of P-loop GTPases and is one of the least characterized member of this family. It is unique because it preferentially hydrolyses ATP rather than GTP, but its physiological role is largely unknown. Studies in different organisms including humans suggest a possible role of YchF in regulating the cellular adaptation to stress conditions. In the current study, we explored the role of YchF in the model organism Escherichia coli. By western blot and promoter fusion experiments, we demonstrate that YchF levels decrease during stress conditions or when cells enter stationary phase. The decline in YchF levels trigger increased stress resistance and cells lacking YchF are resistant to multiple stress conditions, like oxidative stress, replication stress, or translational stress. By in vivo site directed cross-linking we demonstrate that YchF interacts with the translation initiation factor 3 (IF3) and with multiple ribosomal proteins at the surface of the small ribosomal subunit. The absence of YchF enhances the anti-association activity of IF3, stimulates the translation of leaderless mRNAs, and increases the resistance against the endoribonuclease MazF, which generates leaderless mRNAs during stress conditions. In summary, our data identify YchF as a stress-responsive regulator of leaderless mRNA translation.

Cell-autonomous and non-autonomous growth-defective mutants of Drosophila melanogaster

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2365-2375 ◽  
Author(s):  
M. Galloni ◽  
B.A. Edgar
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Cycle Progression ◽  
Growth Regulation ◽  
Larval Growth ◽  
The Body ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Tissue Type ◽  
Growth Defect ◽  
Allelic Series

During animal development, growth of the various tissues and organs that make up the body must be coordinated. Despite recent progress in understanding growth control within the cell unit, the mechanisms that coordinate growth at the organismal level are still poorly understood. To study this problem, we performed a genetic screen for larval growth-defective mutants in Drosophila melanogaster. Characterization of these mutants revealed distinct types of larval growth defects. An allelic series for the translation initiation factor, Eif4A, showed different growth rates and suggests that Eif4A could be used as a dose-dependent growth regulator. Two mutants that fail to exit cellular quiescence at larval hatching (milou and eif4(1006)) have a DNA replication block that can be bypassed by overexpression of the E2F transcription factor. A mutation (bonsai) in a homolog of the prokaryotic ribosomal protein, RPS15, causes a growth defect that is non-cell-autonomous. Our results emphasize the importance of translational regulation for the exit from quiescence. They suggest that the level of protein synthesis required for cell cycle progression varies according to tissue type. The isolation of non-cell-autonomous larval growth-defective mutants suggests that specialized organs coordinate growth throughout the animal and provides new tools for studies of organismal growth regulation.

A Systematic DFT Study of Two Elementary Steps Involving Hydrogen Peroxide and the Hydroxyl Radical in the Fenton Reaction

2018 ◽  
Author(s):  
Danilo Carmona ◽  
David Contreras ◽  
Oscar A. Douglas-Gallardo ◽  
Stefan Vogt-Geisse ◽  
Pablo Jaque ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Hydroxyl Radical ◽  
Ab Initio ◽  
Fenton Reaction ◽  
Basis Set ◽  
Basis Sets ◽  
Dft Methods ◽  
Elementary Steps ◽  
Oxygen Oxygen ◽  
Complete Basis Set

The Fenton reaction plays a central role in many chemical and biological processes and has various applications as e.g. water remediation. The reaction consists of the iron-catalyzed homolytic cleavage of the oxygen-oxygen bond in the hydrogen peroxide molecule and the reduction of the hydroxyl radical. Here, we study these two elementary steps with high-level ab-initio calculations at the complete basis set limit and address the performance of different DFT methods following a specific classification based on the Jacob´s ladder in combination with various Pople's basis sets. Ab-initio calculations at the complete basis set limit are in agreement to experimental reference data and identified a significant contribution of the electron correlation energy to the bond dissociation energy (BDE) of the oxygen-oxygen bond in hydrogen peroxide and the electron affinity (EA) of the hydroxyl radical. The studied DFT methods were able to reproduce the ab-initio reference values, although no functional was particularly better for both reactions. The inclusion of HF exchange in the DFT functionals lead in most cases to larger deviations, which might be related to the poor description of the two reactions by the HF method. Considering the computational cost, DFT methods provide better BDE and EA values than HF and post--HF methods with an almost MP2 or CCSD level of accuracy. However, no systematic general prediction of the error based on the employed functional could be established and no systematic improvement with increasing the size in the Pople's basis set was found, although for BDE values certain systematic basis set dependence was observed. Moreover, the quality of the hydrogen peroxide, hydroxyl radical and hydroxyl anion structures obtained from these functionals was compared to experimental reference data. In general, bond lengths were well reproduced and the error in the angles were between one and two degrees with some systematic trend with the basis sets. From our results we conclude that DFT methods present a computationally less expensive alternative to describe the two elementary steps of the Fenton reaction. However, choice of approximated functionals and basis sets must be carefully done and the provided benchmark allows a systematic validation of the electronic structure method to be employed

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