Penezić Ana Z, Jovanović Vesna B, Pavićević Ivan D, Aćimović Jelena M, Mandić Ljuba M
Department of Biochemistry, Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade 11158, Serbia.
Metallomics. 2015 Oct;7(10):1431-8. doi: 10.1039/c5mt00159e. Epub 2015 Sep 1.
The potential of carbonylation with methylglyoxal to alter HSA's binding affinity for copper(II) ions and its influence on the release of copper(II) ions from copper-HSA complexes were studied. The affinity of HSA to coordinate copper(II) decreased upon carbonylation of the Cys34-SH group. Carbonylation of copper-HSA complexes caused a decrease in Cys34-SH content, conformational changes and the release of copper(II) ions. The ratio between the percentage of reduction in the Cys34-SH group content and the percentage of release of copper(II) from complexes is 2.12 ± 0.28. Because the same ratio (1.96 ± 0.36) was obtained upon oxidation of the Cys34-SH group (with no changes in HSA conformation), the binding/release of copper (II) by HSA depended mainly on the redox state of the Cys34-SH group. The contents of Cys34-SH and HSA-bound copper(II) IONS in the diabetic group (0.457 ± 0.081 mol SH per mol HSA, 10.7 ± 0.01 mmol per mol HSA, resp.) were significantly lower (p < 0.01) compared to the control group (0.609 ± 0.027 mol SH per mol HSA; 13.4 ± 0.01 mmol per mol HSA, resp.). Very strong correlations between the values for HSA-SH and glycated haemoglobin, HbA1c, (R = -0.803, p < 0.01), and between the values for the HSA-bound copper(II) content and HSA-SH content (R = 0.841, p < 0.002) were found in the diabetic group. Thus, HSA carbonylation leads to decrease in HSA-SH content and to the impairment of its copper(II) binding capacity that could contribute to further enhancement of oxidative and carbonyl stress in diabetes (as well as in other diseases with carbonyl stress).
研究了甲基乙二醛羰基化改变人血清白蛋白（HSA）对铜（II）离子结合亲和力的潜力及其对铜 - HSA复合物中铜（II）离子释放的影响。Cys34 - SH基团羰基化后，HSA配位铜（II）的亲和力降低。铜 - HSA复合物的羰基化导致Cys34 - SH含量降低、构象变化以及铜（II）离子释放。Cys34 - SH基团含量降低的百分比与复合物中铜（II）释放百分比之间的比率为2.12±0.28。由于Cys34 - SH基团氧化时获得了相同的比率（1.96±0.36）（HSA构象无变化），HSA对铜（II）的结合/释放主要取决于Cys34 - SH基团的氧化还原状态。与对照组（分别为每摩尔HSA 0.609±0.027摩尔SH；每摩尔HSA 13.4±0.01毫摩尔）相比，糖尿病组中Cys34 - SH和HSA结合的铜（II）离子含量（分别为每摩尔HSA 0.457±0.081摩尔SH，每摩尔HSA 10.7±0.01毫摩尔）显著更低（p < 0.01）。在糖尿病组中发现HSA - SH值与糖化血红蛋白HbA1c之间（R = -0.803，p < 0.01）以及HSA结合的铜（II）含量值与HSA - SH含量值之间（R = 0.841，p < 0.002）存在非常强的相关性。因此，HSA羰基化导致HSA - SH含量降低及其铜（II）结合能力受损，这可能有助于进一步加剧糖尿病（以及其他存在羰基应激的疾病）中的氧化应激和羰基应激。
