4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study

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

doi:10.1016/j.jmgm.2018.11.001

Cited by 20 publications

(16 citation statements)

References 43 publications

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“…However, this protection is not seen in CBD-treated keratinocytes because, as our results indicate, CBD modifies the structure of two of five essential cysteines in Keap1, leading to a decrease in its biological activity. Another explanation for this phenomenon may be the greater affinity of 4-HNE for glutathione than the thioredoxin system components and the interaction with the nucleophilic elements of this active/catalytic centers [56]. That may be confirmed by the decreased level of free 4-HNE in keratinocytes after CBD treatment.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation

Jastrząb

Gęgotek

2019

Cells

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Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is a well-known anti-inflammatory and antioxidant compound. The possibility of its use in cytoprotection of cells from harmful factors, including ultraviolet (UV) radiation, is an area of ongoing investigation. Therefore, the aim of this study was to evaluate the effect of CBD on the regulatory mechanisms associated with the redox balance and inflammation in keratinocytes irradiated with UVA [30 J/cm2] and UVB [60 mJ/cm2]. Spectrophotometric results show that CBD significantly enhances the activity of antioxidant enzymes such as superoxide dismutase and thioredoxin reductase in UV irradiated keratinocytes. Furthermore, despite decreased glutathione peroxidase and reductase activities, CBD prevents lipid peroxidation, which was observed as a decreased level of 4-HNE and 15d-PGJ2 (measured using GC/MS and LC/MS). Moreover, Western blot analysis of protein levels shows that, under stress conditions, CBD influences interactions of transcription factors Nrf2- NFκB by inhibiting the NFκB pathway, increasing the expression of Nrf2 activators and stimulating the transcription activity of Nrf2. In conclusion, the antioxidant activity of CBD through Nrf2 activation as well as its anti-inflammatory properties as an inhibitor of NFκB should be considered during design of new protective treatments for the skin.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation

Jastrząb

Gęgotek

2019

Cells

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“…In particular, it has been demonstrated that direct carbonylation of lateral chains of lysine and arginine residues is equivalent to replacing a hydrophilic residue with a hydrophobic one, which by itself significantly increases the intrinsic aggregation propensity of the protein [38]. More recently, we showed how the indirect carbonylation with 4-hydroxy-2-nonenal induces structural local changes and disturbs the conformational stability, folding and flexibility of oxidized proteins, increasing its lipophilic potential and altering their electrostatic potential [39]. Although we did not discriminate between direct and indirect carbonylation, our results reinforced the participation of protein carbonylation as mediators in mechanisms of resistance to severe malaria in the sickle cell trait.…”

Section: Discussionmentioning

confidence: 99%

Sickle Cell Trait Induces Oxidative Damage on Plasmodium falciparum Proteome at Erythrocyte Stages

Díaz-Castillo

Contreras‐Puentes

Ciro

et al. 2019

IJMS

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The presence of hemoglobin A-S (HbAS) in erythrocytes has been related to the high production of reactive oxygen species (ROS) and an increased in intracellular oxidative stress that affects the progress of Plasmodium erythrocytic cycle life and attenuates its serious clinical symptoms. Nevertheless, oxidative effects on P. falciparum proteome across the intraerythrocytic cycle in the presence of HbAS traits have not been described yet. Here, an immune dot-blot assay was used to quantify the carbonyl index (C.I) on P. falciparum 3D7 proteome at the different asexual erythrocytic stages. Protein carbonylation on parasites cultivated in erythrocytes from two donors with HbAS increased 5.34 ± 1.42 folds at the ring stage compared to control grown in hemoglobin A-A (HbAA) red blood cells. Whereas at trophozoites and schizonts stages were augmented 2.80 ± 0.52 and 3.05 ± 0.75 folds, respectively. Besides proteins involved in processes of the stress response, recognition and invasion were identified from schizonts carbonylated bands by combining SDS-PAGE with MALDI-TOF-TOF analysis. Our results reinforce the hypothesis that such oxidative modifications do not appear to happen randomly, and the sickle cell trait affects mainly a small fraction of parasite proteins particularly sensitive to ROS.

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“…Dataset of Gaff force field parameters were established for three non-standard amino acids (His-HNE, Lys-HNE and Cys-HNE) to be used for molecular dynamics simulations of proteins [1] The framework for derivation of missing bond, angle and dihedral parameters is presented in Fig. 1 .…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…From these datasets, the topology and coordinate of modified proteins were obtained. Hence, the applicability of the newly derived MM parameter, they were subsequently employed in 1 µs MD simulations of each of the three non-natural amino acids treated following the methodology described by [1] and [6] .…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Development and benchmark to obtain AMBER parameters dataset for non-standard amino acids modified with 4-hydroxy-2-nonenal

et al. 2018

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The data described here support the research article “4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study” (Alviz-Amador et al., 2018) . Dataset on Gaff force field parameters of AMBER is provided for assembled three non-standard amino acids resulting of the 4-HNE Michael addition, the main end product of lipids peroxidation. Data include a framework for derivation of missing bonds, angles and dihedral parameters for Cys, His, and Lys modified amino acids, alongside optimized partial charges derived with Restrained Electrostatic Potential (RESP) method and the new force field parameters obtained by quantic mechanical (QM) using HF/6-31G** level of theory. Benchmark as a graphics tutorial summary steps to obtained new parameters and the validation of non-standard amino acids is presented. The new residues constructed are put available to the scientific community to perform molecular dynamics simulations of modified 4-HNE proteins.

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4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study

Cited by 20 publications

References 43 publications

Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation

Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation

Sickle Cell Trait Induces Oxidative Damage on Plasmodium falciparum Proteome at Erythrocyte Stages

Development and benchmark to obtain AMBER parameters dataset for non-standard amino acids modified with 4-hydroxy-2-nonenal

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