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

• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Verfasst von: Staffer, Simone [VerfasserIn]
• Verfasst von: Fricker, Gert [VerfasserIn]
• Verfasst von: Weiskirchen, Ralf [VerfasserIn]
• 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
• Verf.angabe: Wolfgang Stremmel, Simone Staffer, Gert Fricker, Ralf Weiskirchen
• E-Jahr: 2019
• Jahr: 11 November 2019
• Umfang: 8 S.
• Fussnoten: Gesehen am 14.04.2020
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2019
• Band/Heft Quelle: 20(2019,22), Artikel-Nummer 5631, 8 Seiten
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms20225631
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: fatty acids
• Sach-SW: fibrosis
• Sach-SW: inflammation
• Sach-SW: liver
• Sach-SW: NASH
• Sach-SW: steatosis
• Sach-SW: therapy
• Sach-SW: UDCA-PLE
• K10plus-PPN: 1694450392

Abstract

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.