S-nitrosylated human serum albumin-mediated cytoprotective activity is enhanced by fatty acid binding

Yu Ishima, Takaaki Akaike, Ulrich Kragh-Hansen, Shuichi Hiroyama, Tomohiro Sawa, Ayaka Suenaga, Toru Maruyama, Toshiya Kai, Masaki Otagiri

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Binding of oleate to S-nitrosylated human serum albumin (SNO-HSA) enhances its cytoprotective effect on liver cells in a rat ischemia/reperfusion model. It enhances the antiapoptotic effect of SNO-HSA on HepG2 cells exposed to anti-Fas antibody. To identify some of the reasons for the increased cytoprotective effects, additional experiments were performed with glutathione and HepG2 cells. As indicated by 5,5′-dithiobis-2-nitrobenzoic acid binding, the addition of oleate increased the accessibility of the single thiol group of albumin. Binding of increasing amounts of oleate resulted in increasing and more rapid S-transnitrosation of glutathione. Likewise, binding of oleate, or of a mixture of endogenous fatty acids, improved S-denitrosation of SNO-HSA by HepG2 cells. Oleate also enhanced S-transnitrosation by HepG2 cells, as detected by intracellular fluorescence of diaminofluorescein-FM. All of the S-transnitrosation caused by oleate binding was blocked by filipin III. Oleate also increased, in a dose-dependent manner, the binding of SNO-HSA labeled with fluorescein isothiocyanate to the surface of the hepatocytes. A model in two parts was worked out for S-transnitrosation, which does not involve low molecular weight thiols. Fatty acid binding facilitates S-denitrosation of SNO-HSA, increases its binding to HepG2 cells and greatly increases S-transnitrosation by hepatocytes in a way that is sensitive to filipin III. A small nitric oxide transfer takes place in a slow system, which is unaffected by fatty acid binding to SNOHSA and not influenced by filipin III. Thus, fatty acids could be a novel type of mediator for S-transnitrosation.

Original languageEnglish
Pages (from-to)34966-34975
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number50
DOIs
Publication statusPublished - 2008 Dec 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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