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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ullen, A; Fauler, G; Bernhart, E; Nusshold, C; Reicher, H; Leis, HJ; Malle, E; Sattler, W.
Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro.
Free Radic Biol Med. 2012; 53(9):1770-1781
Doi: 10.1016/j.freeradbiomed.2012.08.575
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- Führende Autor*innen der Med Uni Graz
- Sattler Wolfgang
- Üllen Andreas
- Co-Autor*innen der Med Uni Graz
- Bernhart Eva Maria
- Fauler Günter
- Hinteregger Helga
- Leis Hans-Joerg
- Malle Ernst
- Nusshold Christoph
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- Abstract:
- 2-Chlorohexadecanal (2-ClHDA), a chlorinated fatty aldehyde, is formed via attack on ether-phospholipids by hypochlorous acid (HOCl) that is generated by the myeloperoxidase-hydrogen peroxide-chloride system of activated leukocytes. 2-ClHDA levels are elevated in atherosclerotic lesions, myocardial infarction, and neuroinflammation. Neuroinflammatory conditions are accompanied by accumulation of neutrophils (an ample source of myeloperoxidase) in the brain. Microvessel damage by inflammatory mediators and/or reactive oxidants can induce blood-brain barrier (BBB) dysfunction, a pathological condition leading to cerebral edema, brain hemorrhage, and neuronal death. In this in vitro study we investigated the impact of 2-ClHDA on brain microvascular endothelial cells (BMVEC), which constitute the morphological basis of the BBB. We show that exogenously added 2-ClHDA is subject to rapid uptake and metabolism by BMVEC. Using C16 structural analogues of 2-ClHDA we found that the cytotoxic potential decreases in the following order: 2-ClHDA>hexadecanal>palmitic acid>2-ClHDA-dimethylacetal. 2-ClHDA induces loss of barrier function, mitochondrial dysfunction, apoptosis via activation of caspase 3, and altered intracellular redox balance. Finally we investigated potential protective effects of several natural polyphenols on in vitro BBB function. Of the compounds tested, phloretin almost completely abrogated 2-ClHDA-induced BMVEC barrier dysfunction and cell death. These data suggest that 2-ClHDA has the potential to induce BBB breakdown under inflammatory conditions and that phloretin confers protection in this experimental setting.
- Find related publications in this database (using NLM MeSH Indexing)
- Aldehydes - metabolism
- Animals -
- Apoptosis - drug effects
- Brain - blood supply
- Capillary Permeability - drug effects
- Cell Survival - drug effects
- Cells, Cultured -
- Cytoprotection -
- Endothelial Cells - drug effects
- Half-Life -
- Kinetics -
- Microvessels - cytology
- Mitochondria - drug effects
- Palmitic Acid - pharmacology
- Phloretin - pharmacology
- Phlorhizin - pharmacology
- Primary Cell Culture -
- Swine -
- Find related publications in this database (Keywords)
- Chlorinative stress
- Hypochlorite
- Myeloperoxidase
- 2-CIHDA
- Blood-brain barrier
- Free radicals