TGF-ß1 up-regulates the mRNA for the Na+/Ca2+ exchanger in neonatal rat cardiac myocytes

CARRILLO C; CAFFERATA EGA; O’REILLY M; ROBERTS AB; SPORN M; SANTA COLOMA TA

CELLULAR AND MOLECULAR BIOLOGY

Año: 1998 vol. 44 p. 543 - 551

0145-5680

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.