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.