Hypochlorous acid-induced heme degradation from lactoperoxidase as a novel mechanism of free iron release and tissue injury in inflammatory diseases

Carlos Eduardo A. Souza, Dhiman Maitra, Ghassan M. Saed, Michael P. Diamond, Arlindo A. Moura, Subramaniam Pennathur, Husam M. Abu-Soud

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Lactoperoxidase (LPO) is the major consumer of hydrogen peroxide (H 2O 2) in the airways through its ability to oxidize thiocyanate (SCN -) to produce hypothiocyanous acid, an antimicrobial agent. In nasal inflammatory diseases, such as cystic fibrosis, both LPO and myeloperoxidase (MPO), another mammalian peroxidase secreted by neutrophils, are known to co-localize. The aim of this study was to assess the interaction of LPO and hypochlorous acid (HOCl), the final product of MPO. Our rapid kinetic measurements revealed that HOCl binds rapidly and reversibly to LPO-Fe(III) to form the LPO-Fe(III)-OCl complex, which in turn decayed irreversibly to LPO Compound II through the formation of Compound I. The decay rate constant of Compound II decreased with increasing HOCl concentration with an inflection point at 100 μM HOCl, after which the decay rate increased. This point of inflection is the critical concentration of HOCl beyond which HOCl switches its role, from mediating destabilization of LPO Compound II to LPO heme destruction. Lactoperoxidase heme destruction was associated with protein aggregation, free iron release, and formation of a number of fluorescent heme degradation products. Similar results were obtained when LPO-Fe(II)-O 2, Compound III, was exposed to HOCl. Heme destruction can be partially or completely prevented in the presence of SCN -. On the basis of the present results we concluded that a complex bi-directional relationship exists between LPO activity and HOCl levels at sites of inflammation; LPO serve as a catalytic sink for HOCl, while HOCl serves to modulate LPO catalytic activity, bioavailability, and function.

Original languageEnglish (US)
Article numbere27641
JournalPloS one
Volume6
Issue number11
DOIs
StatePublished - Nov 22 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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