Tauroursodeoxycholic acid mobilizes alpha-PKC after uptake in human HepG2 hepatoma cells.
Eur J Clin Invest
; 32(6): 437-42, 2002 Jun.
Article
em En
| MEDLINE
| ID: mdl-12059989
ABSTRACT
BACKGROUND:
Tauroursodeoxycholic acid (TUDCA) may exert anticholestatic effects via Ca(++)- and alpha-protein kinase C (alpha-PKC)-dependent apical vesicular insertion of canalicular transporters in cholestatic hepatocytes (Hepatology 2001; 33 1206-16). Tauroursodeoxycholic acid is mainly taken up into liver cells by Na(+)-taurocholate cotransporting polypeptide (Ntcp). Tauroursodeoxycholic acid selectively translocates alpha-PKC, a key mediator of regulated exocytosis, to hepatocellular membranes. It is unclear whether TUDCA exerts its effects on alpha-PKC after carrier-mediated uptake into liver cells or by interaction with extracellular/membraneous structures. MATERIALS ANDMETHODS:
Human hepatoblastoma HepG2 cells lacking Ntcp were stably transfected with pcDNA3.1/Ntcp or sham-transfected with pcDNA3.1 [+]. Distribution of alpha-PKC was studied using a Western blotting technique. Uptake of [(3)H]taurocholic acid (TCA) was determined radiochemically.RESULTS:
[(3)H]taurocholic acid uptake was approximately 180-fold higher in Ntcp-transfected than in sham-transfected cells. Phorbol 12-myristate 13-acetate (1 micromol L(-1); positive control) increased membrane binding of alpha-PKC by 34% in Ntcp-transfected and by 37% in sham-transfected cells. Tauroursodeoxycholic acid (10 micromol L(-1)) increased membrane-associated alpha-PKC by 19% in Ntcp-transfected, but not in sham-transfected cells (-13%). Taurocholic acid (10 micromol L(-1)) did not affect the distribution of alpha-PKC.CONCLUSION:
Carrier-mediated uptake is a prerequisite for TUDCA-induced translocation of alpha-PKC to hepatocellular membranes.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Ácido Tauroquenodesoxicólico
/
Proteína Quinase C
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Proteínas de Transporte
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Hepatócitos
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Isoenzimas
Limite:
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article