TY  - JOUR
A1  - Jaschke, Alexander
A1  - Chung, Bomee
A1  - Hesse, Deike
A1  - Kluge, Reinhart
A1  - Zahn, Claudia
A1  - Moser, Markus
A1  - Petzke, Klaus-Jürgen
A1  - Brigelius-Flohé, Regina
A1  - Puchkov, Dmytro
A1  - Koepsell, Hermann
A1  - Heeren, Joerg
A1  - Joost, Hans-Georg
A1  - Schürmann, Annette
T1  - The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium
JF  - Human Molecular Genetics
N2  - The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium. Mice lacking Arfrp1 specifically in the intestine \((Arfrp1^{vil−/−})\) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. \(Arfrp1^{vil−/−}\) enterocytes as well as Arfrp1 mRNA depleted Caco-2 cells absorbed fatty acids normally but secreted chylomicrons with a markedly reduced triacylglycerol content. In addition, the release of apolipoprotein A-I (ApoA-I) was dramatically decreased, and ApoA-I accumulated in the \(Arfrp1^{vil−/−}\) epithelium, where it predominantly co-localized with Rab2. The release of chylomicrons from Caco-2 was markedly reduced after the suppression of Rab2, ARL1 and Golgin-245. Thus, the GTPase ARFRP1 and its downstream proteins are required for the lipidation of chylo­microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells.
KW  - ARF
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125658
VL  - 21
IS  - 14
ER  - 
TY  - JOUR
A1  - Neuhaus, Winfried
A1  - Burek, Malgorzata
A1  - Djuzenova, Cholpon C
A1  - Thal, Serge C
A1  - Koepsell, Hermann
A1  - Roewer, Norbert
A1  - Förster, Carola Y
T1  - Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the up-regulation of glucose uptake after subsequent reoxygenation in brain endothelial cells
N2  - During stroke the blood–brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7- fold after 6 h OGD, which was significantly reduced by 10 μM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after 6 h OGD and was still higher (210%) after the 20 h reoxygenation phase compared to normoxia. Ten micromolar MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.
KW  - Blut-Hirn-Schranke
KW  - Schlaganfall
KW  - Glucosetransportproteine
KW  - NMDA-Antagonist
KW  - NMDA-Rezeptor
KW  - blood-brain barrier
KW  - MK801
KW  - NMDAR
KW  - stroke
KW  - glut1
KW  - sglt1
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67241
ER  -