| Autor: |
Irene, Schilcher, Gerhard, Ledinski, Snježana, Radulović, Seth, Hallström, Thomas, Eichmann, Tobias, Madl, Fangrong, Zhang, Gerd, Leitinger, Dagmar, Kolb-Lenz, Barbara, Darnhofer, Ruth, Birner-Gruenberger, Christian, Wadsack, Dagmar, Kratky, Gunther, Marsche, Saša, Frank, Gerhard, Cvirn |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Biochimica et biophysica acta. Molecular and cell biology of lipids |
| ISSN: |
1879-2618 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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