Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Navigation/Suche
- Forscher*innen
- Institutionen
- Projekte
- Publikationen
- Partner
- Geldgeber
- Ausstattung
- Knowhow
- Forschungsfelder
"Köpfe" der aktuellen Meldungen:
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Geier, A; Dietrich, CG; Trauner, M; Gartung, C.
Extrahepatic cholestasis downregulates Oatp1 by TNF-alpha signalling without affecting Oatp2 and Oatp4 expression and sodium-independent bile salt uptake in rat liver.
Liver Int. 2007; 27(8):1056-1065
Doi: 10.1111/j.1478-3231.2007.01523.x
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Trauner Michael
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Hepatic uptake of bile salts is mediated by sodium-dependent and sodium-independent transport systems. During extrahepatic cholestasis, both the function and the expression of the Na(+)/taurocholate cotransporting polypeptide (Ntcp) are downregulated. To test whether sodium-independent organic anion-transporting polypeptides are also affected by extrahepatic cholestasis, the function and expression of all three Oatps have been determined in common bile duct-ligated (CBDL) rats. Oatp1/Oatp1a1 protein mass remained unchanged after CBDL for 1 day, but then declined by 75+/-7% and 90+/-17%, respectively, after 3 and 7 days. In contrast, Oatp2/Oatp1a4 and Oatp4/Oatp1b2 protein expression was not affected by CBDL as compared with controls. After CBDL, Oatp1 mRNA was rapidly downregulated by 68+/-21% of untreated controls (P<0.05) within 24 h, and remained at similar levels at 3 and 7 days. Cytokine-inactivation studies with etanercept pretreatment demonstrated that TNF-alpha-dependent signals mediated the down-regulation of this transporter gene at both protein and mRNA levels during obstructive cholestasis. Sodium-independent uptake of taurocholate and cholate into freshly isolated hepatocyte suspensions showed neither significant differences in K(m) nor V(max) values. These results indicate that sodium-independent transport of bile salts may be mediated by Oatp2 and 4 during biliary obstruction, because its expression remains unaffected and may compensate for loss of Oatp1 expression and function in cholestatic hepatocytes.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cholates - metabolism
- Cholestasis, Extrahepatic - metabolism
- Common Bile Duct - surgery
- Disease Models, Animal -
- Down-Regulation -
- Immunoglobulin G - pharmacology
- Ligation -
- Liver - drug effects Liver - metabolism
- Male -
- Organic Anion Transporters - metabolism
- Organic Anion Transporters, Sodium-Independent - genetics Organic Anion Transporters, Sodium-Independent - metabolism
- RNA, Messenger - metabolism
- Rats -
- Rats, Sprague-Dawley -
- Receptors, Tumor Necrosis Factor -
- Signal Transduction - drug effects
- Sodium - metabolism
- Taurocholic Acid - metabolism
- Time Factors -
- Tumor Necrosis Factor-alpha - antagonists and inhibitors Tumor Necrosis Factor-alpha - metabolism
- Find related publications in this database (Keywords)
- bile acid transporter
- biliary obstruction
- cytokines
- gene regulation