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Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases

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Authors
Nagumo, K.
Tanaka, M.
Chuang, Victor
Setoyama, H.
Watanabe, H.
Yamada, N.,
Kubota, K.
Tanaka, M.
Matsushita, K.
Yoshida, A.
Jinnouchi, H.
Anraku, M.
Kadowaki, D.
Ishima, Y.
Sasaki, Y.
Otagiri, M.
Maruyama, T.
Date
2014
Type
Journal Article

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Nagumo, Kohei and Tanaka, Motohiko and Chuang, Victor Tuan Giam and Setoyama, Hiroko and Watanabe, Hiroshi and Yamada, Naoyuki and Kubota, Kazuyuki and Tanaka, Motoko and Matsushita, Kazutaka and Yoshida, Akira and Jinnouchi, Hideaki and Anraku, Makoto and Kadowaki, Daisuke and Ishima, Yu and Sasaki, Yutaka and Otagiri, Masaki and Maruyama, Toru. 2014. Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases. PloS one. 9 (1): pp. 1-9.
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PloS one
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2014 Nagumo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment.