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SHR Neuro Krebs Kardio Lipid

Schilcher, I; Ledinski, G; Radulović, S; Hallström, S; Eichmann, T; Madl, T; Zhang, F; Leitinger, G; Kolb-Lenz, D; Darnhofer, B; Birner-Gruenberger, R; Wadsack, C; Kratky, D; Marsche, G; Frank, S; Cvirn, G.
Endothelial lipase increases antioxidative capacity of high-density lipoprotein.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019; 1864(10):1363-1374 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Birner-Grünberger Ruth
Cvirn Gerhard
Darnhofer Barbara
Frank Saša
Hallström Seth
Kratky Dagmar
Ledinski Gerhard
Leitinger Gerd
Madl Tobias
Marsche Gunther
Radulovic Snjezana
Schilcher Irene Rosa Maria
Wadsack Christian
Zhang Fangrong

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Number of Figures: 7
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Endothelial lipase (EL) is a strong determinant of structural and functional properties of high-density lipoprotein (HDL). We examined whether the antioxidative capacity of HDL is affected by EL. EL-modified HDL (EL-HDL) and control EV-HDL were generated by incubation of HDL with EL- overexpressing or control HepG2 cells. As determined by native gradient gel electrophoresis, electron microscopy, and small-angle X-ray scattering EL-HDL is smaller than EV-HDL. Mass spectrometry revealed an enrichment of EL-HDL with lipolytic products and depletion of phospholipids and triacylglycerol. Kinetics of conjugated diene formation and HPLC-based malondialdehyde quantification revealed that EL-HDL exhibited a significantly higher resistance to copper ion-induced oxidation and a significantly higher capacity to protect low-density lipoprotein (LDL) from copper ion-induced oxidation when compared to EV-HDL. Depletion of the lipolytic products from EL-HDL abolished the capacity of EL-HDL to protect LDL from copper ion-induced oxidation, which could be partially restored by lysophosphatidylcholine enrichment. Proteomics of HDL incubated with oxidized LDL revealed significantly higher levels of methionine 136 sulfoxide in EL-HDL compared to EV-HDL. Chloramine T (oxidizes methionines and modifies free thiols), diminished the difference between EL-HDL and EV-HDL regarding the capacity to protect LDL from oxidation. In absence of LDL small EV-HDL and EL-HDL exhibited higher resistance to copper ion-induced oxidation when compared to respective large particles. In conclusion, the augmented antioxidative capacity of EL-HDL is primarily determined by the enrichment of HDL with EL-generated lipolytic products and to a lesser extent by the decreased HDL particle size and the increased activity of chloramine T-sensitive mechanisms. Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.

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