Oxidation of hemoglobin by lipid hydroperoxide associated with low-density lipoprotein (LDL) and increased cytotoxic effect by LDL oxidation in heme oxygenase-1 (HO-1) deficiency

E. Nagy, V. Jeney, A. Yachie, R. P. Szabó, O. Wagner, G. M. Vercellotti, J. W. Eaton, G. Balla, J. Balla

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Heme-catalyzed oxidation of low-density lipoprotein (LDL) is one of the relevant mechanisms involved in LDL modification. We previously revealed a substantial oxidation of plasma hemoglobin to methemoglobin and a subsequent heme-catalyzed LDL oxidation generating moieties toxic to endothelium in heme oxygenase-1 (HO-1)-deficiency in human. Drawing upon our previous observation we posited a pathway for oxidation of plasma hemoglobin in the HO-1-deficient child involving LDL-associated lipid hydroperoxide. In support, LDL-associated lipid hydroperoxide oxidized ferrohemoglobin to methemoglobin - known to readily release its heme moieties - in a dose-dependent manner. Repeated heme exposure of the child's LDL further increased its lipid hydroperoxide content within min leading to additional cytotoxic effect on endothelium. Both cytotoxicity and HO-1 inducing ability of the oxidized LDL were strongly dependent on its lipid hydroperoxide content. We wondered if cells of the HO-1-deficient patient were prone to oxidative damage arising from heme-mediated oxidation of LDL. Indeed, we found elevated cytotoxicity induced by heme-catalyzed oxidation of LDL in lymphoblastoid cells derived from the HO-1-deficient patient. We conclude that oxidation of hemoglobin to methemoglobin by LDL-associated lipid hydroperoxide and increased sensitivity of cells of the HO-1-deficient child to stress of oxidized LDL might contribute to the vascular disorders reported earlier.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalCellular and molecular biology
Volume51
Issue number4
DOIs
Publication statusPublished - Sep 30 2005

Keywords

  • Heme
  • Heme oxygenase-1 (HO-1) deficiency
  • Hemoglobin
  • Lipid hydroperoxide
  • Oxidized LDL

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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