The Thiol Group Reactivity and the Antioxidant Property of Human Serum Albumin Are Controlled by the Joint Action of Fatty Acids and Glucose Binding

The binding of ubiquitous serum ligands (free fatty acids) to human serum albumin (HSA) or its glycation can affect thiol group reactivity, thus influencing its antioxidant activity. The effects of stearic acid (SA) and glucose binding on HSA structural changes and thiol group content and reactivity were monitored by fluoroscopy and the Ellman method during a 14-day incubation in molar ratios to HSA that mimic pathophysiological conditions. Upon incubation with 5 mM glucose, HSA glycation was the same as HSA without it, in three different HSA:SA molar ratios (HSA:SA- 1:1-2-4). The protective effect of SA on the antioxidant property of HSA under different glucose regimes (5-10-20 mM) was significantly affected by molar ratios of HSA:SA. Thiol reactivity was fully restored with 5–20 mM glucose at a 1:1 HSA:SA ratio, while the highest thiol content recovery was in pathological glucose regimes at a 1:1 HSA:SA ratio. The SA affinity for HSA increased significantly (1.5- and 1.3-fold, p < 0.01) with 5 and 10 mM glucose compared to the control. These results deepen the knowledge about the possible regulation of the antioxidant role of HSA in diabetes and other pathophysiological conditions and enable the design of future HSA-drug studies which, in turn, is important for clinicians when designing information-based treatments.Article processing charge of 2610 CHF was covered by the joint effort of authors by combining their reviewers vouchers to cover the total APC

Supplementary data for the article: Uzelac, T. N.; Nikolić-Kokić, A. L.; Spasić, S. D.; Mačvanin, M. T.; Nikolić, M. R.; Mandić, L. M.; Jovanović, V. B. Opposite Clozapine and Ziprasidone Effects on the Reactivity of Plasma Albumin SH-Group Are the Consequence of Their Different Binding Properties Dependent on Protein Fatty Acids Content. Chemico-Biological Interactions 2019, 311. https://doi.org/10.1016/j.cbi.2019.108787

Supplementary material for: [https://www.sciencedirect.com/science/article/pii/S0009279719310257?via%3Dihub]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3333]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3865

Sustained paranoid psychosis in a patient with mast cell leukemia and decreased serotonin level

Antipsychotic drugs interfere with the antioxidant defense system provoking complex and often toxicological effects. Here we examined differences in plasma albumin reduced free thiol (SH) group content and its reactivity as a consequence of clozapine (CLZ) and ziprasidone (ZIP) binding. Chronic administration of CLZ reduced, whereas treatment with ZIP increased albumin-SH content in rats. Regardless of the ratio of stearic acid (SA) bound to protein, in vitro binding of ZIP to human serum albumin (HSA) increased both the SH group level and reactivity. In contrast, the effect of CLZ on HSA-SH reactivity was dependent on HSA to SA molar ratio. CLZ binding was accompanied by an increase in HSA-SH reactivity in samples with normal, but a reduction of its reactivity level with higher SA/HSA ratio, compared to drug-free samples. We demonstrate by steady-state fluorescence quenching studies that an increase in SA binding to HSA is associated with a significant reduction of binding constant for both antipsychotics. In addition, this is the first report of quantitative characterization of ZIP binding to HSA. Our findings suggest that albumin-SH content and reactivity is modulated by ZIP towards an increased antioxidant defense capacity in circulation, as opposed to CLZ, which can contribute to the safer, more effective treatment of schizophrenia.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3335]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3865