Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations

Shigeyuki Miyamura, Tadashi Imafuku, Makoto Anraku, Kazuaki Taguchi, Keishi Yamasaki, Yuna Tominaga, Hitoshi Maeda, Yu Ishima, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama

研究成果: Article

15 引用 (Scopus)

抜粋

On account of its long circulating half-life, human serum albumin (HSA) is susceptible to posttranslational modifications that can alter its functions. Here, we comprehensively compared the degree of posttranslational modifications with the functional impairment of HSA derived from 5 different commercially available albumin preparations and clarified their relationships. We used electrospray ionization-time of flight mass spectrometry to evaluate the degree of posttranslational modification of the entire HSA molecule that was associated with disease development and found that the fraction of Cys34-cysteinylated HSA (Cys-Cys34-HSA), a major form of oxidative modification, varied substantially among the albumin preparations. Meanwhile, no remarkable difference was found in the degree of glycated or N-terminal truncated HSA among the preparations tested. The nonosmotic pressure maintenance functions of HSA, such as its antioxidative and ligand-binding activities significantly differed among the preparations. Interestingly, the alternations of these functions showed a significantly negative correlation only with the Cys-Cys34-HSA fraction. These findings suggest that the Cys-Cys34-HSA fraction, as estimated by electrospray ionization-time of flight mass spectrometry can be used as a predictive marker for the functional impairment of albumin preparations and that it would be preferable to use albumin preparations with higher contents of functionally effective albumin that correspond to a lower degree of cysteinylation of Cys34 in clinical practice.

元の言語English
ページ(範囲)1043-1049
ページ数7
ジャーナルJournal of Pharmaceutical Sciences
105
発行部数3
DOI
出版物ステータスPublished - 2016 3 1
外部発表Yes

    フィンガープリント

ASJC Scopus subject areas

  • Pharmaceutical Science

これを引用

Miyamura, S., Imafuku, T., Anraku, M., Taguchi, K., Yamasaki, K., Tominaga, Y., Maeda, H., Ishima, Y., Watanabe, H., Otagiri, M., & Maruyama, T. (2016). Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations. Journal of Pharmaceutical Sciences, 105(3), 1043-1049. https://doi.org/10.1016/j.xphs.2015.12.015