Redox Albuminomics: Oxidized Albumin in Human Diseases

Colombo, Graziano; Clerici, Marigrazia; Giustarini, Daniela; Rossi, Ranieri; Milzani, Aldo; Dalle‐Donne, Isabella

doi:10.1089/ars.2012.4702

Cited by 128 publications

(143 citation statements)

References 79 publications

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“…9) In addition, the distribution of HSA fractions may be used as a systemic redox marker because HSA is the most abundant protein in ECFs, and, thus, is responsible for the largest fraction of reactive sulfhydryl. 17) Mean value (74.7%) for HMA of young group (male, 21.6 years (n=8)) in this study was similar to that previously reported for young male subjects; 73.2% (22.1 years, n=20) 18) and 76.4% (29.1 years, n=10).…”

Section: Discussionmentioning

confidence: 99%

“…4, a positive correlation was observed between carbonyl formation and thiol oxidation (r=0.840, p<0.001), however, the molecular mechanism responsible for oxidative modification markedly differed; for example, the specific target amino acid residues of proteins in carbonyl formation were Lys residues, 10) whereas that in thiol oxidation was the Cys residue. 9) Therefore, as in the case of thiol oxidative modification of isolated and recombinant HSA products for laboratory use, 11,12) significant amounts of carbonylated albumin in all medical-grade HSA products may be caused by long-time exposure to ROS during the manufacturing, isolation, and storage processes of plasma from human donors, even with special and careful treatments in the pharmaceutical industries. Anraku et al 25) also demonstrated that long-term (ca.10 h) exposure to a specific oxidative agent, 2,2′-azobis(2-amidino-propane) dihydrochloride (AAPH), resulted in a significant increase in the amount of carbonylated HSA obtained from human donors, even in the presence of albumin-specific stabilizers (N-Ac Trp and caprylate).…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress is known to cause molecular modifications in many kinds of proteins. Of these, HSA, which is the most abundant plasma protein in humans, undergoes major post-translational modifications (PTMs) associated with diseases, namely, thiol oxidation 9) and carbonylation. 10) These kinds of chemical modifications may cause the heterogeneity of HSA.…”

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confidence: 99%

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Quantitation of Oxidative Modifications of Commercial Human Albumin for Clinical Use

Takahashi

Terada

Arikawa

et al. 2016

Biological & Pharmaceutical Bulletin

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We investigated the quantitation of oxidative chemical modifications, such as thiol oxidation and carbonylation, in medical-grade human serum albumin (HSA) preparations, in comparison with those of healthy and diseased subjects. Four kinds of HSA products were obtained from three major suppliers in Japan. Eight male collegiate students and six healthy male volunteers were recruited as the young (21.6 years) and older (57.2 years) groups, respectively. Four male stable patients (64.3 years) treated with regular hemodialysis (HD) also enrolled in this study. Quantitative analyses for thiol oxidation and carbonylation were performed using HPLC and spectroscopic methods, respectively. Structural characterization was further investigated by differential scanning calorimetry (DSC) and circular dichroism (CD) spectropolarimetry. Significantly larger amounts of thiol-oxidized and carbonylated HSA products were observed than HSA obtained from healthy subjects. In the structural characterization, the midpoint temperature of the denaturation curve (T m ) analyzed by DSC was relatively high, and may have been caused by the added albumin-specific stabilizers, and CD-resolved secondary structure showed that HSA products had a helical conformation. Commercial HSA products for clinical use have a more thermally stable state and remain in a helix-rich structure, even though their specific amino acids (mainly Cys and Lys residues) are oxidatively modified.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Quantitation of Oxidative Modifications of Commercial Human Albumin for Clinical Use

Takahashi

Terada

Arikawa

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Conformational changes in antibody targets presumably affect epitope binding, resulting in altered depletion efficiencies. Many groups have reported retention of nontargeted proteins, which may be due to homologous epitopes, nonspecific interactions with column matrices, or protein–protein interactions [13,26,31,35,36]. The closely controlled trypsin digestion protocol used here, employing single lots of reagents and enzyme and consistent incubation times, makes this step in and of itself unlikely to be a significant contributor to the variations observed.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the effects of preanalytical variables on the stability of the human plasma proteome

Hassis

Niles

Braten

et al. 2015

Analytical Biochemistry

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High quality clinical biospecimens are vital for biomarker discovery, verification, and validation. Variations in blood processing and handling can affect protein abundances and assay reliability. Using an untargeted LC-MS approach, we systematically measured the impact of preanalytical variables on the plasma proteome. Time prior to processing was the only variable that affected the plasma protein levels. LC-MS quantification showed that preprocessing times <6 h had minimal effects on the immunodepleted plasma proteome, but by 4 days significant changes were apparent. Elevated levels of many proteins were observed, suggesting that in addition to proteolytic degradation during the preanalytical phase, changes in protein structure are also important considerations for protocols using antibody depletion. As to processing variables, a comparison of single- vs double-spun plasma showed minimal differences. After processing, the impact ≤3 freeze–thaw cycles was negligible regardless of whether freshly collected samples were processed in short succession or the cycles occurred during 14–17 years of frozen storage (−80 °C). Thus, clinical workflows that necessitate modest delays in blood processing times or employ different centrifugation steps can yield valuable samples for biomarker discovery and verification studies.

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“…HMA may be an important endogenous antioxidant within the body. Oxidized albumin forms have been shown to serve as early biomarkers for human diseases associated with oxidative stress [11,12] . Increased levels of oxidized albumin levels (high HNA level) have been reported in the serum of patients with end-stage renal disease [13,14] , though little is known about the relationship between the oxidized albumin content of the serum in patients on PD and the peritoneal membrane transport status.…”

mentioning

confidence: 99%

Association between Redox Status of Serum Albumin and Peritoneal Membrane Transport Properties in Patients on Peritoneal Dialysis

Lim

Chen²,

Chen³

et al. 2015

Blood Purif

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Background: Albumin, the most abundant protein in the extracellular fluid, displays an important antioxidant activity. Increased levels of oxidized albumin levels (high human non-mercaptoalbumin (HNA) level) have been reported in the serum of patients with end-stage renal disease. In this study, we attempted to identify the albumin redox status in the serum of patients on peritoneal dialysis (PD) and examined the relationship between these proteins and the transport type of the peritoneal membrane and other clinical and laboratory variables. Methods: We performed a cross-sectional study of a cohort of 80 patients with end-stage renal disease receiving PD. Peritoneal transport characteristics were identified and after peritoneal equilibration test patients were grouped as high (high(H)/high-average (HA) group, n = 31) or low (low (L)/low-average (LA) group, n = 49) transporters. The redox state of human serum albumin was measured using high-performance liquid chromatography. Results: The fraction of human mercaptoalbumin (HMA) showed significantly higher values in patients with high transport status than those with low transport status (f(HMA) 64.0 ± 5.4 and 52.7 ± 10.4%, respectively). Our data showed that the H/HA transport characteristic was associated with lower albumin (3.76 ± 0.48 vs. 4.00 ± 0.35, p < 0.05), and lower levels of advanced oxidized protein product (p = 0.008) when compared with the L/LA type. A correlation analysis showed that there was a positive correlation between dialysate/plasma (D/P) creatinine and f(HMA) levels (r = 0.511, p < 0.0001), as well as hemoglobin levels r = 0.231, p = 0.044 and a negative correlation between D/P creatinine and serum albumin, cholesterol and LDL levels (r = -0.236, p = 0.039; r = -0.237, p = 0.038; r = -0.272, p = 0.018, respectively). Conclusions: This study showed that higher serum levels of reduced albumin f(HMA) appear to be associated with high/high average peritoneal membrane transport characteristics in the incident PD patients.

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Redox Albuminomics: Oxidized Albumin in Human Diseases

Abstract: Application of specific redox proteomics techniques for the characterization of oxidized albumin forms in screening studies is required. A further challenge will be to analyze how these oxidative albumin modifications are related to real impact to the body.

Cited by 128 publications

References 79 publications

Quantitation of Oxidative Modifications of Commercial Human Albumin for Clinical Use

Quantitation of Oxidative Modifications of Commercial Human Albumin for Clinical Use

Evaluating the effects of preanalytical variables on the stability of the human plasma proteome

Association between Redox Status of Serum Albumin and Peritoneal Membrane Transport Properties in Patients on Peritoneal Dialysis

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