Myeloperoxidase-derived chlorinating species induce protein carbamylation through decomposition of thiocyanate and urea: novel pathways generating dysfunctional high-density lipoprotein.

ABSTRACT:

Aims

Protein carbamylation through cyanate is considered as playing a causal role in promoting cardiovascular disease. We recently observed that the phagocyte protein myeloperoxidase (MPO) specifically induces high-density lipoprotein (HDL) carbamylation, rather than chlorination, in human atherosclerotic lesions, raising the possibility that MPO-derived chlorinating species are involved in cyanate formation.

Results

Here, we show that MPO-derived chlorinating species rapidly decompose the plasma components thiocyanate (SCN) and urea, thereby promoting (lipo)protein carbamylation. Strikingly, the presence of physiologic concentrations of SCN completely prevented MPO-induced 3-chlorotyrosine formation in HDL. SCN scavenged a 2.5-fold molar excess of hypochlorous acid, promoti

SUBMITTER: Holzer M 

PROVIDER: S-EPMC3810648 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature