A unique mechanism for thiolation of serum albumins by disulphide molecules

Nakashima, Fumie; Shibata, Takahiro; Uchida, Koji

doi:10.1093/jb/mvz084

Cited by 11 publications

(17 citation statements)

References 46 publications

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“…Both cysteine and homocysteine were identified as the low-molecular-weight thiols bound to HSA, with the levels of S-cysteine being higher than that of homocysteine. Further, the increase in S-thiolated albumin correlates with an impairment of the plasma antioxidant activity, thus suggesting that S-thiolation induced changes in the structure and function of HSA [29], which likely contribute to the progression of the disease. Interestingly, a significant inverse correlation was found between thio-HSA and peak VO 2 , which is considered the most objective functional method to assess the cardiopulmonary exercise capacity due to its ability to be measured reproducibly and to accurately reflect HF severity, as increasingly recognized and endorsed by scientific statements.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, in the extracellular environment, especially in plasma, the thiol compounds are much lower [ 31 ]. Specifically, in human blood, the concentration of total plasma cysteine is 200–300 µmol/L, whereas that of homocysteine is around 10 µmol/L [ 29 ], thus explaining the prevalence of cysteinylation over homocysteinylation on albumin.…”

Section: Discussionmentioning

confidence: 99%

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S-Thiolation Targets Albumin in Heart Failure

et al. 2020

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Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group.In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease of the HSA content in the plasma of HF patients in respect to control subjects, a significant increase of thio-HSA with a concomitant decrease in the reduced form of albumin. Cysteine and, at a lesser extent, homocysteine represent the most abundant thiol bound to HSA. A strong inverse correlation was also observed between cysteine-HSA and peak VO2/kg, an index of oxygen consumption associated with HF severity. Moreover, in HL-1 cardiomyocytes incubated with H2O2, we showed a significant decrease of cell viability in cells treated with thio-HSA in respect to restored native-HSA. In conclusion, we found for the first time that S-thiolation of albumin is increased in the plasma of HF patients and induced changes in the structure and antioxidant function of HSA, likely contributing to HF progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

S-Thiolation Targets Albumin in Heart Failure

et al. 2020

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“…In theory, the side radical of cysteine can be irreversibly oxidised to sulfonic acid (Cys34-S(O)O − O − ); however, according to the literature, the percentage of Cys34 in the form of sulfonic acid in blood plasma is extremely low [ 87 ]. Sulfenic acid can also be converted to disulfide (HSA-S-S-R) by interacting with low-molecular-weight blood plasma thiols (GSH, homocysteine, free cysteine), and then reduced to HSA-SH [ 88 , 89 , 90 ].…”

Section: Albumin Participates In the Redox Modulation Of Blood Plamentioning

confidence: 99%

“…According to other experimental data, however, the interaction of HSA with low-molecular-weight thiols involves not only Cys34 but also some cysteine residues that form disulfide bonds: Cys75, Cys90, Cys91, Cys101, Cys124, Cys200, Cys265, Cys392, Cys487, Cys567 [ 90 , 91 ]. Nakashima et al [ 90 ] proposed a mechanism of albumin cysteines thiolation. According to this model, the free thiol group Cys34 is thiolated first.…”

Section: Albumin Participates In the Redox Modulation Of Blood Plamentioning

confidence: 99%

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

et al. 2020

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As a carrier of many biologically active compounds, blood is exposed to oxidants to a greater extent than the intracellular environment. Serum albumin plays a key role in antioxidant defence under both normal and oxidative stress conditions. This review evaluates data published in the literature and from our own research on the mechanisms of the enzymatic and non-enzymatic activities of albumin that determine its participation in redox modulation of plasma and intercellular fluid. For the first time, the results of numerous clinical, biochemical, spectroscopic and computational experiments devoted to the study of allosteric modulation of the functional properties of the protein associated with its participation in antioxidant defence are analysed. It has been concluded that it is fundamentally possible to regulate the antioxidant properties of albumin with various ligands, and the binding and/or enzymatic features of the protein by changing its redox status. The perspectives for using the antioxidant properties of albumin in practice are discussed.

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“…NTS has the strongest affinity for cobalt, copper, and nickel ions, and Cys34-for gold and platinum [11]. The cysteine residue at position 34 has a free SH group that does not form a disulfide bond and is believed to be a target site for redox modifications of albumin [14].…”

Section: Introductionmentioning

confidence: 99%

Ischemia-Modified Albumin: Origins and Clinical Implications

et al. 2021

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Albumin is one of the most abundant proteins in the body of mammals: about 40% of its pool is located in the intravascular space and the remainder is found in the interstitial space. The content of this multifunctional protein in blood is about 60-65% of total plasma proteins. A decrease in its synthesis or changes of functional activity can destabilize oncotic blood pressure, cause a violation of transporting hormones, fatty acids, metals, and drugs. Albumin properties change under ischemic attacks associated with oxidative stress, production of reactive oxygen species, and acidosis. Under these conditions, ischemia-modified albumin (IMA) is generated that has a reduced metal-binding capacity, especially for transition metals, such as copper, nickel, and cobalt. The method of determining the cobalt-binding capability of HSA was initially proposed to evaluate IMA level and then licensed as an ACB test for routine clinical analysis for myocardial ischemia. Subsequent studies have shown the viability of the ACB test in diagnosing other diseases associated with the development of oxidative stress. This review examines recent data on IMA generation mechanisms, describes principles, advantages, and limitations of methods for evaluation of IMA levels, and provides detailed analysis of its use in diagnostic and monitoring therapeutic efficacy in different diseases.

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A unique mechanism for thiolation of serum albumins by disulphide molecules

Cited by 11 publications

References 46 publications

S-Thiolation Targets Albumin in Heart Failure

S-Thiolation Targets Albumin in Heart Failure

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

Ischemia-Modified Albumin: Origins and Clinical Implications

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