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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Radulović, S; Gottschalk, B; Hörl, G; Zardoya-Laguardia, P; Schilcher, I; Hallström, S; Vujić, N; Schmidt, K; Trieb, M; Graier, WF; Malli, R; Kratky, D; Marsche, G; Frank, S.
Endothelial lipase increases eNOS activating capacity of high-density lipoprotein.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020; 1865(4):158612
Doi: 10.1016/j.bbalip.2020.158612
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- Führende Autor*innen der Med Uni Graz
- Frank Sasa
- Radulovic Snjezana
- Co-Autor*innen der Med Uni Graz
- Gottschalk Benjamin
- Graier Wolfgang
- Hallström Seth
- Hörl Gerd
- Kratky Dagmar
- Malli Roland
- Marsche Gunther
- Schilcher Irene Rosa Maria
- Trieb Markus
- Vujic Nemanja
- Zardoya Laguardia Pablo
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- Abstract:
- Endothelial lipase (EL) changes structural and functional properties of high-density lipoprotein (HDL). HDL is a relevant modulator of endothelial nitric oxide synthase (eNOS) activity, but the effect of EL on HDL induced eNOS-activation has not yet been investigated. Here, we examined the impact of EL-modified HDL (EL-HDL) on eNOS activity, subcellular trafficking, and eNOS- dependent vasorelaxation. EL-HDL and empty virus (EV)-HDL as control were isolated from human serum incubated with EL-overexpressing or EV infected HepG2 cells. EL-HDL exhibited higher capacity to induce eNOS phosphorylation at Ser1177 and eNOS activity in EA.hy 926 cells, as well as eNOS-dependent vasorelaxation of mouse aortic rings compared to control HDL. As revealed by confocal and structured illumination-microscopy EL-HDL-driven induction of eNOS was accompanied by an increased eNOS-GFP targeting to the plasma membrane and a lower eNOS-GFP colocalization with Golgi and mitochondria. Widefield microscopy of filipin stained cells revealed that EL-HDL lowered cellular free cholesterol (FC) and as found by thin-layer chromatography increased cellular cholesterol ester (CE) content. Additionally, cholesterol efflux capacity, acyl-coenzyme A: cholesterol acyltransferase activity, and HDL particle uptake were comparable between EL-HDL and control HDL. In conclusion, EL increases eNOS activating capacity of HDL, a phenomenon accompanied by an enrichment of the plasma membrane eNOS pool, a decreased cell membrane FC and increased cellular CE content. Copyright © 2020. Published by Elsevier B.V.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Line - administration & dosage
- Cell Membrane - metabolism
- Cholesterol - metabolism
- Enzyme Activation - administration & dosage
- Hep G2 Cells - administration & dosage
- Humans - administration & dosage
- Lipase - metabolism
- Lipoproteins, HDL - metabolism
- Nitric Oxide Synthase Type III - metabolism
- Phosphorylation - administration & dosage
- Vasodilation - administration & dosage
- Find related publications in this database (Keywords)
- eNOS
- HDL
- Myography
- Microscopy
- Endothelial lipase