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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1043-1049
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume105
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1
Externally publishedYes

Fingerprint

Post Translational Protein Processing
Serum Albumin
Albumins
Mass Spectrometry
Half-Life
Maintenance
Ligands
Pressure

Keywords

  • albumin preparation
  • antioxidative activity
  • cysteine 34
  • cysteinylation
  • ESI-TOFMS
  • ligand binding

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations. / Miyamura, Shigeyuki; Imafuku, Tadashi; Anraku, Makoto; Taguchi, Kazuaki; Yamasaki, Keishi; Tominaga, Yuna; Maeda, Hitoshi; Ishima, Yu; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru.

In: Journal of Pharmaceutical Sciences, Vol. 105, No. 3, 01.03.2016, p. 1043-1049.

Research output: Contribution to journalArticle

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, vol. 105, no. 3, pp. 1043-1049. https://doi.org/10.1016/j.xphs.2015.12.015
Miyamura, Shigeyuki ; Imafuku, Tadashi ; Anraku, Makoto ; Taguchi, Kazuaki ; Yamasaki, Keishi ; Tominaga, Yuna ; Maeda, Hitoshi ; Ishima, Yu ; Watanabe, Hiroshi ; Otagiri, Masaki ; Maruyama, Toru. / Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations. In: Journal of Pharmaceutical Sciences. 2016 ; Vol. 105, No. 3. pp. 1043-1049.
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