Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Resch, U; Semlitsch, M; Hammer, A; Susani-Etzerodt, H; Walczak, H; Sattler, W; Malle, E.
Hypochlorite-modified low-density lipoprotein induces the apoptotic machinery in Jurkat T-cell lines.
Biochem Biophys Res Commun. 2011; 410(4): 895-900.
Doi: 10.1016/j.bbrc.2011.06.089
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- Führende Autor*innen der Med Uni Graz
- Malle Ernst
- Co-Autor*innen der Med Uni Graz
- Hammer Astrid
- Sattler Wolfgang
- Semlitsch Michaela
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- Abstract:
- Myeloperoxidase is abundantly present in inflammatory diseases where activation of monocytes/macrophages and T-cell-mediated immune response occurs. The potent oxidant hypochlorous acid (HOCl), generated by the myeloperoxidase-H(2)O(2)-chloride system of activated phagocytes, converts low-density lipoprotein (LDL) into a proinflammatory lipoprotein particle. Here, we investigated the apoptotic effect of HOCl-LDL, an in vivo occurring LDL modification, on human T-cell lymphoblast-like Jurkat cells. Experiments revealed that HOCl-LDL, depending on the oxidant:lipoprotein molar ratio, induces apoptosis via activation of caspase-3, PARP cleavage and accumulation of reactive oxygen species. The absence of Fas-associated protein with death domain or caspase-8 in mutant cells did not prevent HOCl-LDL induced apoptosis. In contrast, overexpression of the anti-apoptotic Bcl-2 protein protects Jurkat cells against HOCl-LDL-induced apoptosis and prevents accumulation of reactive oxygen species. We conclude that HOCl-LDL-mediated apoptosis in Jurkat cells follows predominantly the intrinsic, mitochondrial pathway. Insitu experiments revealed that an antibody raised against HOCl-LDL recognized epitopes that colocalize both with myeloperoxidase and CD3-positive T-cells in human decidual tissue where local stimulation of the immune system occurs. We provide convincing evidence that formation of HOCl-modified (lipo)proteins generated by the myeloperoxidase-H(2)O(2)-chloride system contributes to apoptosis in T-cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis - drug effects
- Caspase 3 - genetics
- Fas-Associated Death Domain Protein - genetics
- Humans -
- Hypochlorous Acid - chemistry
- Jurkat Cells -
- Lipoproteins, LDL - chemistry
- Peroxidase - metabolism
- Reactive Oxygen Species - antagonists and inhibitors
- T-Lymphocytes - cytology
- Find related publications in this database (Keywords)
- MPO-H(2)O(2)-halide system
- Placenta
- Oxidized lipoproteins
- Lymphocytes
- Hypochlorite