Lipoprotein lipase gene expression in THP-1 cells.
Lipoprotein lipase (LPL) mRNA levels are under the control of signals that activate phospholipase C, resulting in activation of protein kinase C (PKC) and mobilization of intracellular Ca2+ in the human monocytic leukemia cell line THP-1. Induction of LPL in THP-1 cells appears to be mediated by PKC since it was affected by both phorbol 12-myristate 13-acetate (PMA) and a diacylglycerol analogue. This induction was blocked by the specific PKC inhibitor H-7. Although Ca2+ mobilization by the ionophore A23187 also induced LPL mRNA, the mechanism is most likely independent of activation of the Ca2+/calmodulin protein kinase. Depletion of cells of PKC made them refractory to induction by A23187, suggesting that Ca2+ mobilization acts by activating PKC. Addition of cycloheximide (CHX) to undifferentiated THP-1 cells resulted in a transient increase in steady-state mRNA levels (3-fold). Sustained superinduction of LPL mRNA occurred when PMA and CHX were added simultaneously. These results suggest that the level of LPL mRNA is regulated either by a labile regulatory protein, which represses transcription of the LPL gene, or by a protein affecting mRNA stability.
Department of Medicine, University of Washington, Seattle 98195.
J H
JH
Auwerx
S
S
Deeb
J D
JD
Brunzell
G
G
Wolfbauer
A
A
Chait
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology*; D008071:Lipoprotein Lipase / Q000235:genetics*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D010738:Type C Phospholipases / Q000494:pharmacology
D004075:Diglycerides; D012333:RNA, Messenger; D003513:Cycloheximide; D011493:Protein Kinase C; D008071:Lipoprotein Lipase; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium