Effect of 4-HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with β-Spectrin: A Molecular Dynamics Simulation Study

Alvíz‐Amador, Antistio; Galindo‐Murillo, Rodrigo; Pérez-González, Humberto; Rodríguez-Cavallo, Erika; Vivas‐Reyes, Ricardo; Méndez-Cuadro, Darío

doi:10.1021/acs.jcim.9b00772

Cited by 14 publications

(8 citation statements)

References 38 publications

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“…From a mechanistic perspective, the different morphological changes found through SEM analysis could derive from the rearrangement of the membrane and cytoskeleton proteins [39]. In this regard, it is worthwhile to underline that HNE can accumulate in erythrocytic plasma membrane, can perturbate membrane fluidity, and can form protein adducts with spectrin and other membrane and cytoskeleton proteins in a variety of pathophysiological conditions (diabetes, renal disease, glucose-6-phosphate dehydrogenase deficiency, sickle cell anaemia, and tropical diseases) [40][41][42].…”

Section: Hne Induces Morphological Changes In Human Rbcsmentioning

confidence: 99%

Proeryptotic Activity of 4-Hydroxynonenal: A New Potential Physiopathological Role for Lipid Peroxidation Products

et al. 2020

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Background: Eryptosis is a physiological, apoptosis-like death of injured erythrocytes crucial to prevent premature haemolysis and the pathological sequalae generated by cell-free haemoglobin. When dysregulated, the process is associated to several inflammatory-based pathologies. 4-Hydroxy-trans-2-nonenal (HNE) is an endogenous signalling molecule at physiological levels and, at higher concentrations, is involved in the pathogenesis of several inflammatory-based diseases. This work evaluated whether HNE could induce eryptosis in human erythrocytes. Methods: Measurements of phosphatidylserine, cell volume, intracellular oxidants, Ca++, glutathione, ICAM-1, and ceramide were assessed by flow cytometry. Scanning electron microscopy evaluated morphological alterations of erythrocytes. Western blotting assessed caspases. PGE2 was measured by ELISA. Adhesion of erythrocytes on endothelial cells was evaluated by gravity adherence assay. Results: HNE in the concentration range between 10–100 µM induces eryptosis, morphological alterations correlated to caspase-3 activation, and increased Ca++ levels. The process is not mediated by redox-dependent mechanisms; rather, it strongly depends on PGE2 and ceramide. Interestingly, HNE induces significant increase of erythrocytes adhesion to endothelial cells (ECs) that are in turn dysfunctionated as evident by overexpression of ICAM-1. Conclusions: Our results unveil a new physiopathological role for HNE, provide mechanistic details of the HNE-induced eryptosis, and suggest a novel mechanism through which HNE could exert pro-inflammatory effects.

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Section: Hne Induces Morphological Changes In Human Rbcsmentioning

confidence: 99%

Proeryptotic Activity of 4-Hydroxynonenal: A New Potential Physiopathological Role for Lipid Peroxidation Products

et al. 2020

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“…Where G complex indicates the free energy of the ligand-receptor complex, and G receptor (5-HT 1B ) and G ligand (DMT, serotonin, 112814775, and ERG) are the free energies of isolated protein and ligand in the solvent, respectively following the methodology proposed by Alviz-Amador et al (26). When calculating the Gibbs free energy (ΔG), the entropy contribution of the protein was ignored because the binding energy was used here to determine the relative binding strength of each complex.…”

Section: δG Bind = G Complex − (G Receptor + G Ligand )mentioning

confidence: 99%

In silico study of dimethyltryptamine analogues against 5-HT1B receptor: Molecular docking, dynamic simulations and ADMET prediction

Contreras‐Puentes

Alvíz‐Amador

Manzur-Villalobos

2022

J Herbmed Pharmacol

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Introduction: The 5-HT1B receptor has a potential role in various psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. The objective of this study was to perform docking and molecular dynamics simulation to evaluate at atomic level the behavior of N,N-dimethyltryptamine (DMT) on 5-HT1B receptor.Methods: In this study, initially, a search for DMT was performed using the PubChem database. Subsequently, molecular docking was executed using AutoDock Vina based in PyRx 0.8 with a 95% analogy. Additionally, ergotamine (ERG) and serotonin were used as control. Then, it ran a total of 100 ns molecular dynamics simulations on 5-HT1B bound with DMT, serotonin, 112814775, and ERG. Finally, pharmacokinetic prediction and IV acute toxicity for analogues and DMT were performed.Results: It was possible to show that 112814775 had the lowest binding energy with the receptor. In addition, 112814775 presented great conformational stability, low mobility, and stiffness compared to the control ligands: ERG, serotonin, and DMT subsequent dynamic analysis. With respect to the free energy calculation, contributions such as Van der Waals, electrostatics, and nonpolar interactions for all systems, were highlighted.Conclusion: 112814775 showed affinities with 5-HT1B receptor and evidenced notable behavior by molecular dynamic simulation according to root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), the radius of gyration, number of hydrogen bond, and free energy calculated. These results established the possible relevance of in-silico studies in search of DMT analogues against the 5-HT1B receptor, which may be associated with alterations such as depression and anxiety, and may become future study molecules for the treatment of this type of disorder.

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“…[ 47 ] Previous studies have suggested that the modification of HNE can affect cell cycle events, and is associated with many degenerative diseases, such as Alzheimer's disease, atherosclerosiss, cataract, diabetes, and cancer. [ 48 ] However, the abundance of HNE modified proteins in cell is usually very low, making their detection by MS difficult. In response to this challenge, several enrichment methods for HNE modified protein including immunoaffinity enrichment, and solid phase hydrazine chemical enrichment have been developed.…”

Section: Post‐translational Modification Proteomementioning

confidence: 99%

Discover the Post‐Translational Modification Proteome Using Mass Spectrometry

et al. 2021

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Protein post‐translational modifications (PTMs) are chemical modifications on proteins. PTMs play a key role in many cellular processes by influencing the structure of proteins and dynamically regulating their functions. Therefore, characterizing PTMs at proteome level is critical to provide invaluable insight into the functions of proteins underlying different biological processes. Advances in modern proteomics technologies including sample preparation, chromatography separation as well as mass spectrometry have propelled the PTMs proteome to further depths. During the past decade, to better examine the PTMs with high sensitivity and selectivity, our group have developed a series of MS‐based novel analytical approaches to study the protein PTMs. Herein, we mainly introduce these approaches developed by our group and discuss how to overcome the technical obstacles of studying various protein PTMs with mass spectrometry. What is the most favorite and original method developed in your research group? The qualitative and quantitative approaches developed for analysis of PTM proteome. How do you get into this specific field? Could you please share some experiences with our readers? I entered Fudan University in 2003, when the sequencing of human genome was just completed. At that time, the life science entered the post‐genomic era, the era of proteomics. My post‐doctoral work is mainly based on mass spectrometry analysis, which is the core tool for proteome research. Therefore, I began to develop mass spectrometry‐based method for proteome research since then. What is the most important personality for scientific research? Creative, persistence, and collaboration. What's your hobbies? Playing badminton.

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Effect of 4-HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with β-Spectrin: A Molecular Dynamics Simulation Study

Cited by 14 publications

References 38 publications

Proeryptotic Activity of 4-Hydroxynonenal: A New Potential Physiopathological Role for Lipid Peroxidation Products

Proeryptotic Activity of 4-Hydroxynonenal: A New Potential Physiopathological Role for Lipid Peroxidation Products

In silico study of dimethyltryptamine analogues against 5-HT1B receptor: Molecular docking, dynamic simulations and ADMET prediction

Discover the Post‐Translational Modification Proteome Using Mass Spectrometry

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