Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Holzer, M; Zangger, K; El-Gamal, D; Binder, V; Curcic, S; Konya, V; Schuligoi, R; Heinemann, A; Marsche, G.
Myeloperoxidase-derived chlorinating species induce protein carbamylation through decomposition of thiocyanate and urea: novel pathways generating dysfunctional high-density lipoprotein.
Antioxid Redox Signal. 2012; 17(8):1043-1052
Doi: 10.1089/ars.2011.4403
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Holzer Michael
- Marsche Gunther
- Co-Autor*innen der Med Uni Graz
- Binder Veronika
- Curcic Sanja
- El-Gamal Dalia
- Heinemann Akos
- Konya Viktoria
- Schuligoi Rufina
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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, promoting HDL carbamylation, but not chlorination. Cyanate significantly impaired (i) HDL's ability to activate lecithin-cholesterol acyltransferase; (ii) the activity of paraoxonase, a major HDL-associated anti-inflammatory enzyme; and (iii) the antioxidative activity of HDL. Innovation: Here, we report that MPO-derived chlorinating species preferentially induce protein carbamylation-rather than chlorination-in the presence of physiologically relevant SCN concentrations. The carbamylation of HDL results in the loss of its anti-inflammatory and antioxidative activities. Conclusion: MPO-mediated decomposition of SCN and/or urea might be a relevant mechanism for generating dysfunctional HDL in human disease. Antioxid. Redox Signal. 17, 1043-1052.
- Find related publications in this database (using NLM MeSH Indexing)
- Antioxidants - metabolism
- Chlorine - metabolism
- Humans -
- Hypochlorous Acid - chemistry
- Lipoproteins, HDL - isolation & purification
- Lysine - metabolism
- Peroxidase - metabolism
- Thiocyanates - blood
- Urea - blood