Fatty Acid Binding to Human Serum Albumin in Blood Serum Characterized by EPR Spectroscopy

Haeri, Haleh H.; Schunk, Bettina; Tomaszewski, Jörg; Schimm, Heike; Gelos, Marcos; Hinderberger, Dariush

doi:10.1002/open.201900113

Cited by 24 publications

(60 citation statements)

References 55 publications

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“…Previous studies reported that allosteric changes in HSA may be utilized to reflect critical functional changes in albumin and explored diagnostic and prognostic values of these changes in cancer (17,33). It has also been found that long chain fatty acids binding alters the interactive binding of ligands in the two major drug binding sites of HSA (34).…”

Section: Epr-determined Biophysical Parameters Reflecting Albumin Conformational Changes Are Consistent Predictors Of Covid-19 Mortalitymentioning

confidence: 99%

“…Spin labeled long-chain fatty acids (SLFA) are established probes to explore structural and functional changes in albumin by EPR spectroscopy (16,17). This approach relies on the well-studied ability of albumin to strongly and exclusively bind with fatty acids in blood.…”

Section: Introductionmentioning

confidence: 99%

“…Albumin has at least seven different specific binding sites for long chain fatty acids located in different domains within the protein (18)(19)(20). Effectively, structural and functional changes in HSA may be assessed through the detection of parallel changes in mobility and binding affinity of SLFAs, in addition to the distribution of the spin labels on the albumin molecule (17). EPR spectra of spin labels bound to different domains of the protein provide information on the local fatty acids/protein interactions, which may probe changes in the overall structure of the protein under unfolding or damaging conditions; Fig.…”

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confidence: 99%

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Neutrophil-mediated Oxidative Stress and Albumin Structural Damage Predict COVID-19-associated Mortality

Badawy

Yasseen

El-Messiery

et al. 2021

Preprint

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Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 25 patients who were followed up for a median of 12.5 days (1-35 days), among them 14 had died. Analyzing blood samples from patients and healthy individuals (n=10), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance (EPR) spectra of spin labelled fatty acids (SLFA) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivors HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and greater S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Stratified at the means, Kaplan-Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W<0.16, 80% (9/12) vs. S/W>0.16, 20% (2/10), p=0.008; plasma [H2O2]>7.1 μM, 83.3% (5/6) vs. 16.7% (1/6), p=0.049). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (< 0.0253) predicted mortality with 100% accuracy (100% (6/6) vs. 0% (0/6), logrank χ2 = 12.01, p = 5x10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements.

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Section: Epr-determined Biophysical Parameters Reflecting Albumin Conformational Changes Are Consistent Predictors Of Covid-19 Mortalitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophil-mediated Oxidative Stress and Albumin Structural Damage Predict COVID-19-associated Mortality

Badawy

Yasseen

El-Messiery

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Spin-labeled fatty acids (SLFAs) are established probes to explore structural and functional changes in albumin by EPR spectroscopy ( Ge et al, 1990 ; Haeri et al, 2019 ). This approach relies on the well-studied ability of albumin to strongly and exclusively bind with fatty acids in blood.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality

Badawy

Yasseen

El-Messiery

et al. 2021

eLife

View full text Add to dashboard Cite

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1–35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10–11). Non-survivors’ HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ2=12.1, p=4.9×10−4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.

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“…The long-chain fatty acid-binding ability of albumin can be quantified using electron paramagnetic resonance (EPR) techniques (Jalan et al 2009;Haeri et al 2019). There are seven fatty acid-binding sites on an albumin molecule, of which three have high affinity and the other four have lower affinity.…”

Section: Fatty Acid-binding Capacitymentioning

confidence: 99%

Impaired albumin function: a novel potential indicator for liver function damage?

et al. 2019

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Albumin is the most abundant plasma protein and albumin infusion is commonly used. Conventionally, the biologic and therapeutic effects of albumin have been thought to be due to its oncotic properties. However, albumin has a variety of biologic functions, including molecular transport, anti-oxidation, anti-inflammation, endothelial stabilisation, anti-thrombotic effects, and the adjustment of capillary permeability. Despite this, the functions of albumin have not been thoroughly investigated. Recent studies have shown non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, and liver failure to be associated with impairments in albumin function, which are associated with impairments in liver function and disease prognosis. Post-translational modifications of albumin cause structural modifications that affect protein function. Recently, the concentration of albumin associated with normal function, the 'efficient albumin concentration', has been attracting more interest. In addition, although many biologic markers, including albumin concentration, are widely used for the assessment of early liver dysfunction in patients with liver diseases, the predictive values are unsatisfactory. However, clinical evidence has suggested that albumin function may represent a novel biomarker of early impairment in liver function. In this review, we summarise the factors affecting albumin function and discuss the clinical significance of impairments in albumin function in various liver diseases. KEY MESSAGES1. The importance of albumin depends not only on its concentration, but also on its various physiological functions. 2. Impaired albumin function has been reported in a variety of liver diseases, and is associated with disease severity and prognosis, thereby proposing the concept of 'effective albumin concentration'. 3. Albumin dysfunction occurs earlier than other conventional indicators, and albumin dysfunction may be a new biomarker of early impairment in liver function. 4. Many exogenous and endogenous factors lead to post-translational modifications of albumin, which alters the three-dimensional structure of albumin, resulting in a decrease in its biological activity.

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Fatty Acid Binding to Human Serum Albumin in Blood Serum Characterized by EPR Spectroscopy

Cited by 24 publications

References 55 publications

Neutrophil-mediated Oxidative Stress and Albumin Structural Damage Predict COVID-19-associated Mortality

Neutrophil-mediated Oxidative Stress and Albumin Structural Damage Predict COVID-19-associated Mortality

Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality

Impaired albumin function: a novel potential indicator for liver function damage?

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