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Crosstalk of sterol‐dependent and non‐sterol‐dependent signaling in human monocytes after in vitro addition of LDL
Author(s) -
Seres Ildikó,
Fóris Gabriella,
Kovács Éva,
Páll Dénes,
Varga Zsuzsa,
Balogh Zoltán,
Paragh György
Publication year - 2006
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1346
Subject(s) - protein kinase c , sterol , cholesterol , chemistry , biochemistry , phorbol , inositol , low density lipoprotein , pertussis toxin , receptor , ldl receptor , signal transduction , intracellular , endogeny , microbiology and biotechnology , lipoprotein , biology , g protein
The aim of the present study was to investigate low density lipoprotein (LDL)‐induced, non‐sterol‐dependent signaling and its possible role in cholesterol balance. LDL in 10 µg ml −1 concentration could induce inositol trisphosphate (IP 3 ) and Ca 2+ signal generation through a pertussis toxin (PT) sensitive G protein in human monocytes. The increase in [Ca 2+ ]i was derived from the intracellular pools. LDL also induced activation and translocation of protein kinase C (PKC) into the cell membrane, by processes, which were significantly inhibited in the first 20 min by preincubation with PT and PKC‐inhibitor H‐7. The PKC‐activating phorbol‐12‐myristate‐13‐acetate (PMA), differently from LDL, enhanced the LDL‐receptor (LDL‐R)‐mediated binding and degradation of [ 125 I]LDL, but inhibited endogenous cholesterol synthesis, and both effects were inhibited by H‐7. The LDL‐induced inhibition of binding and degradation of [ 125 I]LDL was not affected by H‐7, whereas decreased cholesterol synthesis was counteracted by H‐7. These results suggest the existence of a non‐sterol‐dependent signal pathway of LDL‐Rs, by which endogenous cholesterol synthesis, that is, the [ 14 C]acetate incorporation, is regulated through PKC activation. Copyright © 2006 John Wiley & Sons, Ltd.