Clinical Implications Associated With the Posttranslational Modification–Induced Functional Impairment of Albumin in Oxidative Stress–Related Diseases

Abstract

Recent research findings indicate that the posttranslational modification of human serum albumin (HSA) such as oxidation, glycation, truncation, dimerization, and carbamylation is related to certain types of diseases. We report herein on a simple and rapid analytical method, using an electrospray ionization time-of-flight mass spectrometry technique, that allows posttranslational modifications of HSA to be quantitatively and qualitatively evaluated with a high degree of sensitivity. In patients with chronic liver disease, chronic renal disease, and diabetes mellitus, an increase in the level of oxidized cysteine-34 (Cys-34) of HSA accompanied by a decrease in the level of reduced Cys-34 was observed. The redox status of Cys-34 was correlated with ligand binding and the antioxidative functions of HSA. Available evidence indicates that monitoring the redox state of Cys-34 not only could be a useful marker for evaluating the progression of disease and its complications but also would permit therapeutic efficacy to be predicted. The redox state of Cys-34 was also used as an index of the quality of HSA preparations. These data suggest that monitoring the posttranslational modifications of HSA can be important, because the function of HSA is related not only to its serum concentration but also to the preservation of its structural integrity under disease conditions.

Methanethiosulfonate Derivative of OX063 Trityl: A Promising and Efficient Reagent for Side‐Directed Spin Labeling of Proteins

“…In healthy subjects, Cys34 is mainly present in a reduced form (≈70 %) (HSA red ), whereas 25 to 30 % is reversibly oxidized (HSA ox ), as a mixed disulfide with cysteine, cysteinylglycine, homocysteine, or GSH (HSAox) . Small amounts (3–4 %) of irreversibly oxidized forms, such as sulfinate and sulfonate, are also found . Under pathologic conditions, such as kidney or liver diseases, the level of oxidized albumin may increase to up to 70 % .…”

“…HSA has 35 cysteine residues; 34 are paired in 17 robust disulfide bonds and only one, cysteine‐34 (Cys34), is readily available for SDSL . In healthy subjects, Cys34 is mainly present in a reduced form (≈70 %) (HSA red ), whereas 25 to 30 % is reversibly oxidized (HSA ox ), as a mixed disulfide with cysteine, cysteinylglycine, homocysteine, or GSH (HSAox) . Small amounts (3–4 %) of irreversibly oxidized forms, such as sulfinate and sulfonate, are also found .…”

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34

“…oxidized albumin) before and after dialysis (0.24 mM and 0.25 mM) while Terawaki et al [15] observed large variations (from 55% to 33%, respectively). By considering that about 90% of the oxidized albumin is represented as the mixed disulfide Cys 34 S-SCys and that the average concentration of albumin is 0.7 mM [4], it results that about 0.1 mM of cysteine is released from the protein to the plasma during about 3 h of dialysis. 1A).…”

“…One curious exception is represented by Cys 34 of HSA, which is the most abundant protein in plasma, reaching the concentration of 0.6-0.8 mM [2]. In healthy subjects, this residue is mainly present in a reduced form (about 70%) (HSA red ) while 25-30% is found as a reversible oxidized form, that is, as mixed disulfide with cysteine and in minor amounts with cysteinylglycine, homocysteine, and GSH (HSA ox ) [3,4]. Cys 34 [2].…”

“…HSA comprises 17 disulfide bonds and one free cysteine, i.e. Irreversible oxidized forms, like sulfinate and sulfonate, are also found in very small amounts (3-4%) [4]. In healthy subjects, this residue is mainly present in a reduced form (about 70%) (HSA red ) while 25-30% is found as a reversible oxidized form, that is, as mixed disulfide with cysteine and in minor amounts with cysteinylglycine, homocysteine, and GSH (HSA ox ) [3,4].…”