Stremmel, Wolfgang
[VerfasserIn];
Staffer, Simone
[VerfasserIn];
Fricker, Gert
[VerfasserIn];
Weiskirchen, Ralf
[VerfasserIn]
The bile acid-phospholipid conjugate ursodeoxycholyl-lysophosphatidylethanolamide (UDCA-LPE) disintegrates the lipid backbone of raft plasma membrane domains by the removal of the membrane phospholipase A2
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Medientyp:
E-Artikel
Titel:
The bile acid-phospholipid conjugate ursodeoxycholyl-lysophosphatidylethanolamide (UDCA-LPE) disintegrates the lipid backbone of raft plasma membrane domains by the removal of the membrane phospholipase A2
Beschreibung:
The bile acid-phospholipid conjugate ursodeoxycholyl-lysophosphatidylethanolamide (UDCA-LPE) was shown to have anti-inflammatory, antisteatotic, and antifibrotic properties, rendering it as a drug targeting non-alcoholic steatohepatitis (NASH). On a molecular level, it disrupted the heterotetrameric fatty acid uptake complex localized in detergent-resistant membrane domains of the plasma membrane (DRM-PM). However, its mode of action was unclear. Methodologically, UDCA-LPE was incubated with the liver tumor cell line HepG2 as well as their isolated DRM-PM and all other cellular membranes (non-DRM). The membrane cholesterol and phospholipids were quantified as well as the DRM-PM protein composition by Western blotting. The results show a loss of DRM-PM by UDCA-LPE (50 µM) with a 63.13 ± 7.14% reduction of phospholipids and an 81.94 ± 8.30% reduction of cholesterol in relation to mg total protein. The ratio of phospholipids to cholesterol changed from 2:1 to 4:1, resembling those of non-DRM fractions. Among the members of the fatty acid uptake complex, the calcium-independent membrane phospholipase A2 (iPLA2β) abandoned DRM-PM most rapidly. As a consequence, the other members of this transport system disappeared as well as the DRM-PM anchored fibrosis regulating proteins integrin β-1 and lysophospholipid receptor 1 (LPAR-1). It is concluded that UDCA-LPE executes its action by iPLA2β removal from DRM-PM and consequent dissolution of the raft lipid platform.