抄録
Cardiac Na+/Ca2+ exchanger1 (NCX1) expression levels change under various pathophysiological conditions, e.g. heart failure. However, its mechanism is unknown. We previously showed that fluvastatin (Flv), an HMG-CoA reductase (HMGR) inhibitor, decreased NCX1 mRNA and protein expression via inhibiting a small G-protein, RhoB in H9c2 cardiomyoblasts. Flv-induced down-regulation of NCX1 mRNA was reversed by mevalonate, farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP), suggesting an involvement of isoprenylation of RhoB. Conversely, we also found that lisophosphatidylcholine (LPC) increased NCX1 mRNA and protein by activating RhoB. RhoB requires isoprenylation for its activation by either GGPP or FPP. Here, we investigated which isoprenoid is involved in NCX1 increasing effect of LPC. Treatment of H9c2 cells with Flv for 24 hours decreased NCX1 mRNA to about 60% of control. Addition of GGPP or FPP restored NCX1 mRNA, which had been decreased by Flv, to a control level within 24 hours. No significant difference was observed between GGPP and FPP. When LPC was applied with Flv, NCX1 mRNA remained decreased. However, when LPC and GGPP were applied simultaneously, NCX1 mRNA was increased to a level significantly higher than the control. Unlike GGPP, FPP did not induce this increase. These results suggest that an isoprenoid involved in the effect of LPC increasing NCX1 mRNA is GGPP but not FPP. [J Physiol Sci. 2006;56 Suppl:S126]
