Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

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 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bernhart Eva Maria
Fauler Günter
Leis Hans-Jörg
Malle Ernst
Nusshold Christoph
Reicher Helga
Sattler Wolfgang
Üllen Andreas
Altmetrics:

Dimensions Citations:

Plum Analytics:
Number of Figures: 8
| | | | | | | |
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
© Meduni Graz Impressum