Oxidative Damage in Aliphatic Amino Acids and Di- and Tripeptides by the Environmental Free Radical Oxidant NO3•: The Role of the Amide Bond Revealed by Kinetic and Computational Studies

2019 ◽  
Vol 84 (6) ◽  
pp. 3405-3418 ◽  
Author(s):  
Joses G. Nathanael ◽  
Uta Wille
Keyword(s):  
Amino Acids ◽  
Free Radical ◽  
Oxidative Damage ◽  
Amide Bond ◽  
Computational Studies

scholarly journals Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

Activation of Mitochondrial STAT3 Increases Mitochondrial Respiration and Inhibits Oxidative Stress in Chronic Lymphocytic Leukemic Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 287-287 ◽  
Author(s):  
Li Jia ◽  
Nadiha Uddin ◽  
John G. Gribben
Keyword(s):  
Cell Death ◽  
Free Radical ◽  
Oxidative Damage ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Mitochondrial Mass ◽  
Free Radical Generation ◽  
Atp Turnover ◽  
Radical Generation

Abstract Abstract 287 Chronic lymphocytic leukemia (CLL) is a malignant disease occurring in the elderly and remains incurable. CLL is characterized by resistance to both spontaneous and induced apoptosis aided by changes induced by the tumor microenvironment. STAT3 is a signal responsive transcription factor that plays pivotal roles in tumorigensis in a number of malignancies including CLL. STAT3 resides in an inactive form in the cytoplasm of non-stimulated cells and in response to various cytokines and growth factors present in the microenvironment is activated through JAK-mediated phosphorylation of two residues, tyrosine 705 (Y705) and serine 727 (S727). Phosphorylation of this critical tyrosine residue (Y705) induces STAT3 dimerization through phosphotyrosine-SH2 domain interaction and. once dimerized, enters the nucleus and activates a broad array of target genes. The role of serine phosphorylation (S727) is less understood. It has been reported that STAT3 is constitutively phosphorylated on S727 and pS727-STAT3, not pY705-STAT3, binds DNA and activates transcription in CLL cells. However, it has also been reported that STAT3 is present in the mitochondria both in cell lines and primary liver and heart of mouse models, where it is one of the components of the mitochondrial electron transport chain (mETC) and plays an important role in mitochondrial respiration. The active form of mitochondrial STAT3 is pS727-STAT3 and it is crucial for Ras-dependent transformation by sustaining altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. It is unknown whether STAT3 regulates mitochondrial function in CLL. We therefore investigated whether activated STAT3 regulates mitochondrial respiration in CLL and whether it is important for CLL cell survival. Screening by Western blotting in untreated CLL patients' samples (n=16 )revealed that both pS727-STAT3 and pY705-STAT3 were constitutively expressed and we demonstrated correlation of the expression levels between these two active forms. Using fluorescent microscopy and cellular protein fractionation, both pS727-STAT3 and pY705-STAT3 showed mitochondrial localization in CLL cells. Stimulation of CLL cells with IL-10 induced STAT3 activation and both active forms of STAT3 exhibited mitochondrial translocation. The JAK inhibitor AG490 prevented STAT3 translocation to the mitochondria and led to reduction of mitochondrial mass and expression of cytochrome c oxidase IV (COX IV), one of the components of mETC. Knockdown of STAT3 RNA also decreased COX IV expression. Flow cytometry studies demonstrated that activation of STAT3 by IL-10 prevented depolarization of mitochondrial membrane potential and free radical generation by CLL cells, but inhibition of STAT3 induced mitochondrial oxidative damage and CLL cell death. The role of STAT3 activation by IL-10 on mitochondrial respiration was determined using a Seahorse XF Extracellular Flux Analyzer and demonstrated significantly increased coupled and uncoupled mitochondrial respiration and ATP turnover. Inhibition of STAT3 by AG490 reduced mitochondrial respiration and ATP turnover. However, decreased mitochondrial respiration did not provoke glycolytic capacity in CLL cells, indicating that CLL cells mainly rely on mitochondria for energetic needs. In summary, we demonstrate that activated STAT3 targets mitochondria and increases mitochondrial respiration and ATP turnover in CLL cells. This enables increased bioenergetic mitochondrial function and also prevents oxidative damage of CLL cells. Inhibition of STAT3 reduces mitochondrial mass and function but increases free radical generation and promotes CLL cell death. We therefore propose that mitochondrial STAT3 could be a therapeutic target for the treatment of CLL. Disclosures: Gribben: Roche: Honoraria; Celgene: Honoraria; GSK: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria.

The role of chelating agents and amino acids in preventing free radical formation in bleaching systems

2018 ◽  
Vol 129 ◽  
pp. 194-201
Author(s):  
Jing Hodes ◽  
Patric Sielaff ◽  
Hendrik Metz ◽  
Daniela Kessler-Becker ◽  
Thomas Gassenmeier ◽  
...  
Keyword(s):  
Amino Acids ◽  
Free Radical ◽  
Chelating Agents ◽  
Radical Formation ◽  
Free Radical Formation

scholarly journals Deuterium Incorporation Protects Cells from Oxidative Damage

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Piero Sestili ◽  
Maurizio Brigotti ◽  
Cinzia Calcabrini ◽  
Eleonora Turrini ◽  
Valentina Arfilli ◽  
...  
Keyword(s):  
Free Radical ◽  
Oxidative Damage ◽  
Genomic Instability ◽  
Protein Damage ◽  
Deuterium Incorporation ◽  
Cold Environments ◽  
Free Radical Chemistry ◽  
Cellular Components ◽  
Oxidative Attack

In the cold environments of the interstellar medium, a variety of molecules in which a hydrogen (H) atom has been replaced by its heavier isotope deuterium (D) can be found. From its emergence, life had to counteract the toxic action of many agents, which posed a constant threat to its development and propagation. Oxygen-reactive species are archaic toxicants that lead to protein damage and genomic instability. Most of the oxidative lesions involve cleavage of C-H bonds and H abstraction. According to free radical chemistry principles, the substitution of D for H in oxidation-sensitive positions of cellular components should confer protection against the oxidative attack without compromising the chemical identity of the compounds. Here, we show that deuterated nucleosides and proteins protect from oxidative damage. Our data suggest a new, subtle but likely role of D in terrestrial life’s evolution in that its inclusion in critical biomolecules might have facilitated their resistance during the infinite generations of life entities, cells, and organisms.

Mechanical Properties of Biopolymer Chains

1992 ◽  
Vol 292 ◽  
Author(s):  
Ruth Pachter ◽  
Peter D. Haaland ◽  
Robert L. Crane ◽  
W. Wade Adams
Keyword(s):  
Mechanical Properties ◽  
Amino Acids ◽  
Hydrogen Bonding ◽  
Molecular Hydrogen ◽  
Mechanical Response ◽  
Amide Bond ◽  
Pivotal Role ◽  
Helical Structures ◽  
Naturally Occurring

AbstractMolecular simulations that predict the molecular mechanical response of alpha-helical biopolymers with a reinforcing intra-molecular hydrogen bonding network, viz,, a ‘spring-like’ behavior, are presented in this study. Mechanical properties of extended biopolymer strands based on naturally occurring amino acids, namely poly(L-A1a) and for comparison poly(LGlu), versus synthetic PPTA containing an amide bond, are compared to those assuming alpha-helical structures. Thus, the pivotal role of such motifs in biological systems utilizing superior compressive mechanical properties can be inferred.

Role of amino acids and micronutrients on biosynthesis of spiramycins

1981 ◽  
Vol 31 (1) ◽  
pp. 189-193 ◽  
Author(s):  
Mohamed A. Ashy ◽  
Abd El-Galil ◽  
M. Khalil ◽  
Abou-Zeid A. Abou-Zeid
Keyword(s):  
Amino Acids

Directive Effect of Chain Length in Modulating Peptide Nano-assemblies

2020 ◽  
Vol 27 (9) ◽  
pp. 923-929
Author(s):  
Gaurav Pandey ◽  
Prem Prakash Das ◽  
Vibin Ramakrishnan
Keyword(s):  
Electron Microscopy ◽  
Amino Acids ◽  
Light Scattering ◽  
Chain Length ◽  
Self Assembly ◽  
The Self ◽  
Ionic Charge ◽  
Self Assembling ◽  
Biophysical Techniques

Background: RADA-4 (Ac-RADARADARADARADA-NH2) is the most extensively studied and marketed self-assembling peptide, forming hydrogel, used to create defined threedimensional microenvironments for cell culture applications. Objectives: In this work, we use various biophysical techniques to investigate the length dependency of RADA aggregation and assembly. Methods: We synthesized a series of RADA-N peptides, N ranging from 1 to 4, resulting in four peptides having 4, 8, 12, and 16 amino acids in their sequence. Through a combination of various biophysical methods including thioflavin T fluorescence assay, static right angle light scattering assay, Dynamic Light Scattering (DLS), electron microscopy, CD, and IR spectroscopy, we have examined the role of chain-length on the self-assembly of RADA peptide. Results: Our observations show that the aggregation of ionic, charge-complementary RADA motifcontaining peptides is length-dependent, with N less than 3 are not forming spontaneous selfassemblies. Conclusion: The six biophysical experiments discussed in this paper validate the significance of chain-length on the epitaxial growth of RADA peptide self-assembly.

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