Carrillo C, Cafferata E G, Genovese J, O'Reilly M, Roberts A B, Santa-Coloma T A
Instituto de Investigaciones Bioquímicas Fundación Campomar, Buenos Aires, Argentina.
Cell Mol Biol (Noisy-le-grand). 1998 May;44(3):543-51.
Northern analyses of neonatal cardiac myocytes demonstrated that TGF-beta1 (5 ng/ml) stimulates and IL-1beta (5 ng/ml) decreases the steady-state levels of the mRNA coding for the Na+/Ca2+ exchanger. This is in agreement with the effects of TGF-beta1 and IL-1beta on beating rate and calcium uptake, suggesting that such effects might be mediated, at least partially, through up-regulation of the Na+/Ca2+ exchanger. Basal and TGF-beta1 stimulated mRNA levels were inhibited by the PKC inhibitors H7 (10 microM) and GF109203X (250 nM). In addition, apigenin (12.5 microM), a MAP kinase inhibitor, was able to inhibit basal mRNA levels for the exchanger. Cycloheximide (35.5 microM) had no effect on basal mRNA levels for the exchanger but steady-state levels were diminished in cells treated with TGF-beta1. Finally, actinomycin D (10 microM) inhibited both basal and TGF-beta1 stimulated mRNA levels, though with a more pronounced effect in the presence of TGF-beta1. These results suggest that a complex mechanism of regulation exists for the exchanger and that PKC and possibly MAP kinases might be involved. The up-regulation of this important protein for calcium extrusion, induced by TGF-beta1, might prepare cells to better overcome the calcium overload which occurs under cellular stress and might explain some of the cytoprotective effects of TGF-beta1.
对新生心肌细胞的Northern分析表明，转化生长因子β1（5纳克/毫升）可刺激而白细胞介素-1β（5纳克/毫升）会降低编码钠/钙交换体的mRNA的稳态水平。这与转化生长因子β1和白细胞介素-1β对搏动率和钙摄取的影响一致，表明这种影响可能至少部分是通过钠/钙交换体的上调介导的。蛋白激酶C抑制剂H7（10微摩尔）和GF109203X（250纳摩尔）可抑制基础水平以及转化生长因子β1刺激的mRNA水平。此外，促分裂原活化蛋白激酶抑制剂芹菜素（12.5微摩尔）能够抑制交换体的基础mRNA水平。放线菌酮（35.5微摩尔）对交换体的基础mRNA水平没有影响，但在用转化生长因子β1处理的细胞中，稳态水平降低。最后，放线菌素D（10微摩尔）可抑制基础水平以及转化生长因子β1刺激的mRNA水平，不过在存在转化生长因子β1的情况下作用更明显。这些结果表明，交换体存在复杂的调控机制，蛋白激酶C以及可能的促分裂原活化蛋白激酶可能参与其中。转化生长因子β1诱导的这种对钙外排很重要的蛋白质的上调，可能使细胞更好地克服细胞应激时发生的钙超载，这可能解释了转化生长因子β1的一些细胞保护作用。
