Modulation of the reactivity of the thiol of human serum albumin and its sulfenic derivative by fatty acids

Torres, Marı́a José; Turell, Lucía; Botti, Horacio; Antmann, Laura; Carballal, Sebastián; Ferrer-Sueta, Gerardo; Radí, Rafael; Álvarez, Beatriz

doi:10.1016/j.abb.2012.03.011

Cited by 49 publications

(61 citation statements)

References 50 publications

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“…Mixed disulfides were prepared by incubating reduced HSA (ϳ1 mM) overnight with the disulfide of interest (up to 20 mM) in acetate buffer (100 mM, pH 4.5, 0.1 mM diethylenetriaminepentaacetic acid (DTPA), 4°C) or tris buffer (100 mM, pH 7.4, 0.1 mM DTPA, 4°C). The pH of the buffer was chosen so as to favor maximum displacement of equilibria toward mixed disulfide formation as follows: acidic pH when the pK a of the leaving thiol was higher than that of HSA-SH (8.1 (23,25)) as in the case of Hcy-Hcy, GSSG, and HED, and basic pH when the pK a was lower (DTNB, CysOMeCysOMe) (27). The mixed disulfides were subjected to gel filtration in a PD-10 column (GE Healthcare) equilibrated with phosphate buffer (100 mM, pH 7.4, 0.1 mM DTPA), and the yield of disulfide was quantified by subtraction of HSA-SH concentration before and after treatment with LMW disulfides.…”

Section: Methodsmentioning

confidence: 99%

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Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide

Cuevasanta

Lange

Bonanata

et al. 2015

Journal of Biological Chemistry

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Background:Hydrogen sulfide (H 2 S) modulates physiological processes in mammals. Results: The reactivity of H 2 S toward disulfides (RSSR) and albumin sulfenic acid (RSOH) to form persulfides (RSSH) was assessed. Conclusion: H 2 S is less reactive than thiols. Persulfides have enhanced nucleophilicity. Significance: This kinetic study helps rationalize the contribution of the reactions with oxidized thiol derivatives to H 2 S biology.

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Section: Methodsmentioning

confidence: 99%

“…They are typically unstable and decay mainly through reaction with a second thiol to form disulfides. Because HSA forms a long-lived and well characterized sulfenic acid (24,25), it could open the way to kinetic measurements of the reactions with H 2 S. In addition, HSA could potentially also form a stable persulfide (HSA-SSH).…”

mentioning

confidence: 99%

Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide

Cuevasanta

Lange

Bonanata

et al. 2015

Journal of Biological Chemistry

Self Cite

281

344

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“…The free thiol group of albumin, present at a concentration of 0.6 mM in plasma, constitutes the largest pool of reactive thiols in plasma and acts as a key oxidant scavenger. [19][20][21] Therefore, some physiological conditions (e.g. exercise, fasting) and diseases (hemodialysis, preeclampsia, diabetes) which are associated with oxidative stress, tend to increase the amount of FA bound to HSA, 19 which could be a protective adaptation.…”

Section: Influence Of Stearic Acid On the Reactivity Of Hsa-shmentioning

confidence: 99%

“…22 Binding of FA is associated with significant structural changes in the HSA molecule, 23 which can cause the Cys34 residue to be more or less exposed to the surrounding environment, leading to differential reactivity and susceptibility to oxidative stress. [19][20][21][24][25][26][27] These findings lead to the question: Does the binding of EL and ED to HSA (for which the antioxidant effect is proven) influence HSA-SH reactivity and therefore its antioxidant potential? Although numerous studies on the interactions between polyphenols and HSA have been performed, the changes in HSA-SH reactivity that can occur upon polyphenol binding (which may be relevant to antioxidant properties) have not been considered yet.…”

Section: Introductionmentioning

confidence: 99%

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Binding of enterolactone and enterodiol to human serum albumin: increase of cysteine-34 thiol group reactivity

et al. 2016

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The interaction of polyphenolic molecules with human serum albumin (HSA) could lead to changes in the reactivity of the HSA Cys34 thiol group (HSA-SH). The influences of enterolactone (EL) and enterodiol (ED) binding on HSA-SH reactivity in fatty acid (FA)-free HSA, and in HSA with bound stearic acid (S) in S/HSA molar ratios of 1 : 1 and 4 : 1, were investigated by the determination of the pseudo first order rate constants (k') for the thiol reaction with 5,5'-dithiobis-(2-nitrobenzoic acid). The binding affinities and binding sites of EL and ED were also determined, using fluorescence measurements of the intrinsic fluorescence ). When the S/HSA ratio was increased, the binding affinities and number of binding sites for EL and ED were decreased. At the same time, a high correlation between binding constants and increased Cys34 reactivity was found (r = 0.974). Competitive experiments using diazepam indicated that the binding of ED and of EL was located in the hydrophobic pocket of site II in HSA. Overall, it is evident that stearic acid could modulate the enterolignan effects on HSA-SH reactivity as well as their binding to HSA. This finding could be important for pharmacokinetics and the expression of enterolignan antioxidant effects in vivo after an intake of lignan rich food.

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Identification of novel disulfide adducts between the thiol containing leaving group of the nerve agent VX and cysteine containing tripeptides derived from human serum albumin

Kranawetvogl

Küppers

Gütschow

et al. 2017

Drug Testing and Analysis

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Chemical warfare agents represent a continuous and considerable threat to military personnel and the civilian population. Such compounds are prohibited by the Chemical Weapons Convention, to which adherence by the member states is strictly controlled. Therefore, reliable analytical methods for verification of an alleged use of banned substances are required. Accordingly, current research focuses on long-term biomarkers derived from covalent adducts with biomolecules such as proteins. Recently, we have introduced a microbore liquid chromatography/electrospray ionization high-resolution tandem mass spectrometry method allowing for the investigation of two different classes of adducts of the nerve agent VX with human serum albumin (HSA). Phosphonylated tyrosine residues and novel disulfide adducts at cysteine residues of HSA were produced by enzymatic cleavage with pronase and detected simultaneously. Notably, the thiol containing leaving group of VX (2-(diisopropylamino)ethanethiol, DPAET) formed disulfide adducts that were released as cysteine and proline containing dipeptides originating from at least two different sites of HSA. Aim of this study was to identify assumed and novel adducts of DPAET with HSA using synthetic peptide reference compounds. Two novel tripeptides were identified representing disulfide adducts with DPAET (Met-Pro-Cys-DPAET, MPC-DPAET and Asp-Ile-Cys-DPAET, DIC-DPAET). MPC-DPAET was shown to undergo partial in-source decay during electrospray ionization for MS detection thereby losing the N-terminal Met residue. This results in the more stable Pro-Cys-DPAET (PC-DPAET) dipeptide detectable as protonated ion. The limit of detection for MPC-DPAET was evaluated, revealing toxicologically relevant VX plasma concentrations. The results provide novel insights into the reactivity of VX and its endogenous targets. Copyright © 2016 John Wiley & Sons, Ltd.

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Modulation of the reactivity of the thiol of human serum albumin and its sulfenic derivative by fatty acids

Cited by 49 publications

References 50 publications

Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide

Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide

Binding of enterolactone and enterodiol to human serum albumin: increase of cysteine-34 thiol group reactivity

Identification of novel disulfide adducts between the thiol containing leaving group of the nerve agent VX and cysteine containing tripeptides derived from human serum albumin

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