Abstract
Expression of the cardiac Na+/Ca2+ exchanger1 (NCX) changes under various pathophysiological conditions but the mechanism is not known. Recently found that in H9c2 cardiomyoblasts fluvastatin (Flv), an HMG-CoA reductase (HMGR) inhibitor, decreased NCX mRNA and protein. This effect of Flv was prevented by the presence of either farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP), which are isoprenoids required for small GTP-binding protein signaling. Here, we examined the role of small GTP-binding proteins in the regulation of NCX mRNA levels in H9c2 cells. Intracellular expression of C3 toxin, a Rho-GTPase inhibitor, decreased NCX mRNA. Conversely, lisophosphatidylcholine (LPC), a Rho-mediated signaling activator, increased NCX mRNA in a C3 toxin-sensitive manner. However, overexpression of constitutive active or dominant negative mutants of RhoA did not affect NCX mRNA. RT-PCR analysis demonstrated that H9c2 cells expressed not only RhoA but also RhoB, which is isoprenylated by either FPP or GGPP. Western blot analysis showed that membrane associated RhoB was decreased by Flv, but increased by LPC. When transcription was blocked by 5,6-dichlorobenzimidazole riboside, NCX mRNA stability was decreased by Flv, but increased by LPC. These results suggest that Rho-family protein, most probably RhoB, is involved in stabilizing NCX mRNA in cardiac myocytes [Jpn J Physiol 55 Suppl:S96 (2005)]
