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Tyrosine residues of bovine serum albumin play an important role in protecting SH-SY5Y cells against heme/H2O2/NO2−-induced damage

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Abstract

Serum albumin (SA) has been shown to act as a heme scavenger in hemolysis and can protect cell against the toxic effect of heme. However, the mechanism of SA in heme detoxification is not well understood. Interestingly, increasing studies indicate that heme/H2O2-dependent reaction is unlikely to be the principal cause of heme toxicity in excessive intravascular hemolysis conditions. Moreover, high levels of NO2− and NO3− were also found in patients with severe hemolytic diseases, which seem to involve in heme toxic effect as well. Therefore, we proposed that studying the protection mechanism of SA against the heme/H2O2/NO2−-induced cytotoxicity may be more consistent with free heme-associated disorder pathologies. In this study, we tested the hypotheses that tyrosine residues of bovine serum albumin (BSA) play a prominent role in detoxifying heme in SH-SY5Y cells. Both BSA and tyrosine modified BSA (BSA-T) were used to explore this protective mechanism. Most of cellular injury (oxidative and nitrative damage) induced by heme/H2O2/NO2− were prevented by pretreatment with an equimolar concentration of BSA or BSA-T, and BSA was found more efficient than BSA-T. Meanwhile, BSA or BSA-T binding to heme is not accompanied by a decrease of heme’s peroxidase activity. Collectively, these data suggest that the protecting effect of BSA against heme-induced damage in the intravascular hemolysis diseases is not accomplished by preventing the primary reactivity of heme with H2O2, but by trapping radical through special residues such as tyrosine to render other important protein less damaged.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 31570810 and 31770866), Natural Science Foundation of Hubei Scientific Committee (No. 2016CFA001), and the Fundamental Research Funds for the Central Universities of China (2017KFYXJJ167).

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  1. Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of China

    Peipei Wang, Jinming Wu, Zhonghong Gao & Hailing Li

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  1. Peipei Wang
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Correspondence to Hailing Li.

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Wang, P., Wu, J., Gao, Z. et al. Tyrosine residues of bovine serum albumin play an important role in protecting SH-SY5Y cells against heme/H2O2/NO2−-induced damage. Mol Cell Biochem 454, 57–66 (2019). https://doi.org/10.1007/s11010-018-3452-3

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