Auwerx J H, Deeb S, Brunzell J D, Wolfbauer G, Chait A
Department of Medicine, University of Washington, Seattle 98195.
Biochemistry. 1989 May 30;28(11):4563-7. doi: 10.1021/bi00437a009.
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.
脂蛋白脂肪酶（LPL）的mRNA水平受激活磷脂酶C的信号调控，这会导致蛋白激酶C（PKC）的激活以及人单核细胞白血病细胞系THP-1中细胞内Ca2+的动员。THP-1细胞中LPL的诱导似乎是由PKC介导的，因为它受到佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）和二酰基甘油类似物的影响。这种诱导被特异性PKC抑制剂H-7阻断。尽管离子载体A23187引起的Ca2+动员也诱导了LPL mRNA，但该机制很可能独立于Ca2+/钙调蛋白蛋白激酶的激活。细胞中PKC的耗尽使其对A23187的诱导产生抗性，表明Ca2+动员通过激活PKC起作用。向未分化的THP-1细胞中添加环己酰亚胺（CHX）会导致稳态mRNA水平短暂升高（3倍）。当同时添加PMA和CHX时，LPL mRNA会持续超诱导。这些结果表明，LPL mRNA的水平要么受一种不稳定的调节蛋白调控，该蛋白抑制LPL基因的转录，要么受一种影响mRNA稳定性的蛋白调控。
