Modulation of protein kinase C by taurolithocholic acid in isolated rat hepatocytes
Open Access
- 1 February 1999
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 29 (2), 477-482
- https://doi.org/10.1002/hep.510290227
Abstract
The protein kinase C (PKC) family of isoenzymes plays a key role in the regulation of hepatocellular secretion. The hydrophobic and cholestatic bile acid, taurolithocholic acid (TLCA), acts as a potent Ca++ agonist in isolated hepatocytes. However, its effect on PKC isoforms has not been elucidated. Here we investigate the effects of TLCA at low micromolar concentrations on the distribution of PKC isoforms and on membrane‐associated PKC activity. The distribution of PKC isoforms was determined in isolated rat hepatocytes in short‐term culture using Western blotting and immunofluorescence techniques. PKC activity was measured radiochemically. TLCA (10 μmol/L) induced selective translocation of ε‐PKC by 47.9% ± 20.5% (P < .02 vs. controls; n = 7), but not of α‐, δ‐, and ζ‐PKC to the hepatocellular membranes, whereas the phorbol ester, phorbol 12‐myristate 13‐acetate (PMA) (1 μmol/L) caused translocation of all mobile isoforms, α‐, δ‐, and ε‐PKC, as shown by immunoblotting. Immunofluorescence studies demonstrated selective translocation of ε‐PKC to the canalicular membranes of isolated rat hepatocyte couplets by TLCA (10 μmol/L), but predominant translocation to intracellular and basolateral membranes by PMA (1 μmol/L). Both TLCA (10 μmol/L) and PMA (1 μmol/L) stimulated membrane‐bound PKC activity by 60.5% ± 45.8% (P < .05 vs. controls; n = 5) and 72.4% ± 37.2% (P < .05; n = 5), respectively. TLCA at lower concentrations (5 μmol/L) was less effective. Because activation of ε‐PKC has been associated with impairment of vesicle‐mediated targeting and insertion of membrane proteins in secretory cells, it is attractive to speculate that TLCA reduces bile secretory capacity of the liver cell by activation of ε‐PKC at the canalicular membraneThis publication has 28 references indexed in Scilit:
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