Cellular uptake mechanisms and responses to NO transferred from mono-and poly-S-nitrosated human serum albumin

Yu Ishima, Fumika Yoshida, Ulrich Kragh-Hansen, Kaori Watanabe, Naohisa Katayama, Keisuke Nakajou, Takaaki Akaike, Toshiya Kai, Toru Maruyama, Masaki Otagiri

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19 Citations (Scopus)

Abstract

Endogenous S-nitrosated human serum albumin (E-Mono-SNO-HSA) is a large molecular weight nitric oxide (NO) carrier in human plasma, which has shown many beneficial effects in different animal models. To construct more efficient SNO-HSA preparations, SNO-HSA with many conjugated SNO groups has been prepared using chemical modification (CM-Poly-SNO-HSA). We have compared the properties of such a preparation to those of E-Mono-SNO-HSA. Cellular uptake of NO from E-Mono-SNO-HSA partly takes place via low molecular weight thiol, and it results in cytoprotective effects by induction of heme oxygenase-1. By contrast, transfer of NO from CM-Poly-SNO-HSA into the cells is faster and more pronounced. The influx mainly takes place by cell-surface protein disulfide isomerase. The considerable NO inflow results in apoptotic cell death by ROS induction and caspase-3 activation. Thus, increasing the number of SNO groups on HSA does not simply intensify the cellular responses to the product but can also result in very different effects.

Original languageEnglish
Pages (from-to)1196-1206
Number of pages11
JournalFree Radical Research
Volume45
Issue number10
DOIs
Publication statusPublished - 2011 Oct 1
Externally publishedYes

Keywords

  • Apoptosis
  • Cell-surface protein disulfide isomerase
  • Cytoprotection
  • Nitric oxide
  • S-nitrosation

ASJC Scopus subject areas

  • Biochemistry

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    Ishima, Y., Yoshida, F., Kragh-Hansen, U., Watanabe, K., Katayama, N., Nakajou, K., Akaike, T., Kai, T., Maruyama, T., & Otagiri, M. (2011). Cellular uptake mechanisms and responses to NO transferred from mono-and poly-S-nitrosated human serum albumin. Free Radical Research, 45(10), 1196-1206. https://doi.org/10.3109/10715762.2011.606814