We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Effect of phorbol ester and platelet-derived growth factor on protein kinase C in rat hepatic stellate cells.
- Authors
Kobayashi, Yoshimasa; Bridle, Kim R.; Ramm, Grant A.; O'Neill, Rosemary; Britton, Robert S.; Bacon, Bruce R.
- Abstract
Background/Aims: Hepatic stellate cells (HSC) play a key role in hepatic fibrogenesis and thus, it is important to understand the intracellular signalling pathways that influence their behaviour. This study investigated the expression and regulation of protein kinase C (PKC) in HSC. Results: Western blot analysis indicates that rat HSC express at least four PKC isoforms, PKC-α, PKC-δ, PKC-ℇ and PKC-ζ. PKC-α and PKC-ζ were located predominantly in the cytosol and were redistributed to the membrane by the PKC agonist, phorbol 12-myristate 13-acetate (PMA), while PKC-δ and PKC-ℇ were highly membrane-bound and did not undergo translocation by PMA. PKC-α, PKC-δ and PKC-ζ were rapidly downregulated by PMA. However, PKC-ℇ was resistant to downregulation. We also examined phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS), a specific substrate of PKC, as another approach to assess activation of PKC. Platelet-derived growth factor (PDGF) and PMA increased the phosphorylation of MARCKS, suggesting that PDGF can induce PKC activation. PDGF-induced stimulation of extracellular signal-regulated kinase, phosphatidylinositol 3-kinase and p70-S6 kinase was not abrogated by downregulation of PKC-α, PKC-δ and PKC-ζ. Prolonged PKC inhibition did not inhibit the fibrogenic phenotype. Conclusion: Multiple PKC isoforms are expressed in rat HSC and are differentially regulated by PMA. PDGF activates certain mitogenic signalling pathways independent of PKC-α, PKC-δ and PKC-ζ. Specific PKC isoforms may modulate different cell functions in HSC.
- Subjects
PHORBOL esters; PLATELET-derived growth factor; PROTEIN kinase C; KUPFFER cells; LIVER cells; LABORATORY rats
- Publication
Liver International, 2007, Vol 27, Issue 8, p1066
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/j.1478-3231.2007.01573.x