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The role of PKC in shaping intracellular Ca2+ oscillations in hepatocytes
Author(s) -
Bartlett Paula Jane,
Metzger Walson,
Gaspers Lawrence D,
Thomas Andrew P
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1117.13
Subject(s) - protein kinase c , intracellular , phosphorylation , microbiology and biotechnology , chemistry , biophysics , biology
In hepatocytes hormone‐induced frequency‐modulated intracellular Ca 2+ oscillations (osc) control multiple signalling events. IP 3 and Ca 2+ oscillate synchronously but the question remains, are Ca 2+ osc controlled by Ca 2+ feedback on the IP 3 receptor (IP 3 R) or is Ca 2+ dependent +ve and/or −ve feedback on IP 3 levels also required? Ca 2+ imaging techniques were used to study Ca 2+ osc in 24h cultured primary hepatocytes. Activation and inhibition of PKC decreased Ca 2+ osc frequency and PLC activity induced by hormone. Photolysis of caged‐IP 3 resulted in transient Ca 2+ release with Ca 2+ osc observed in 40% of cells. These IP 3 generated osc in the absence of hormone presumably arise via repetitive Ca 2+ induced Ca 2+ release from the IP 3 R. However, FRET probes sensitive to changes in IP 3 are currently under study to assess whether Ca 2+ released by caged‐IP 3 is able to feedback on PLC and regenerate IP 3 . IP 3 R channel opening can be modulated by phosphorylation. Downregulation of PKC did not affect caged‐IP 3 ‐induced Ca 2+ osc occurrence or frequency, whilst acute activation of PKC increased Ca 2+ osc frequency. These data suggest under basal conditions the IP 3 R is not regulated by PKC phosphorylation but hormone‐induced PKC activity may affect IP 3 R opening. This study provides evidence that multiple PKC isoenzymes exert counteracting effects to shape hormone‐induced Ca 2+ osc. (Thomas P. Infusino Endowment to APT)