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Human serum albumin (HSA) in human blood system is a significant target of oxidative stress, and severe alterations to its physiological functions can result from severe oxidative damage. The severe oxidative damage to HSA has been associated with various human diseases, including liver diseases, chronic kidney disease, cardiovascular disease, neurodegenerative disorders and cancer. As such, HSA was investigated as a potential biomarker for estimating various types of oxidative stress-induced damage to human health in this study. The fluorescence quenching methodology was employed and optimized to estimate the oxidative damage level of HSA reliably and reproducibly. Specifically, the fluorescence quenching approach relied on the intrinsic fluorescence of HSA based on its single tryptophan residue, located at position 214 (TRP 214) and proved effective in estimating severe oxidative damage to human health. Molecular modelling was employed to identify the most oxidizable amino acid residues in HSA, with TRP 214 found to play a crucial role in certain oxidative stressors that cause severe oxidative damage to HSA. The levels of kynurenine, a metabolite in the tryptophan pathway induced by its severe oxidative damage, have been found to be elevated in patients diagnosed with venous thromboembolism (VTE). Such an elevation is associated with a higher risk of recurrence and mortality. Kynurenine, an endogenous metabolite of tryptophan, has been implicated in the pathogenesis and progression of VTE due to its multifaceted procoagulant effects [1]. These effects comprise activation of platelets, stimulation of tissue factor expression, and inhibition of fibrinolysis. The significance of VTE, VITT (Vaccine-induced immune thrombotic thrombocytopenia), and thrombosis in global health is emphasized by the importance of continued research and innovation in this field, not only in South Korea but also worldwide including Germany. Based on the molecular modelling and experiment results of this research, oxidative stressors exhibited a stronger affinity with HSA and this is mainly depending on the presence of oxidizable amino-acid residues in HSA. Especially, TRP 214 exerts the crucial role for the severe oxidative damage of HSA. Hence, the specific metabolites produced from TRP214 in HSA induced by severe oxidative damage were estimated reliably and effectively based on the optimum analytical methodologies in this research, which can have great potential as prethrombotic diagnosis technology for VTE and VITT prevention and treatment.
References
- Voils 2018: doi.org/10.1016/j.thromres.2018.03.003
| Keywords | Human Serum Albumin, Biomarker, Oxidative Damage, TRP214, Kynurenine, Venous Thromboembolism, Prethrombotic Diagnosis |
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