Thiazolidinediones影響胎盤第二新型有機陽離子轉運蛋白 (OCTN2)表現之機轉探討

Abstract

Carnitine is important for the transfer of acry-carnitine with long-chain fatty acids, which is then transported into mitochondria for β-oxidation. The fetus cannot synthesize adequate amount of carnitine, and the active transfer of carnitine from the mother to the fetus is important. The novel organic cation transporter 2 (OCTN2) is a high-affinity carnitine transporter. In current study, we investigate the effects of thiazolidinediones on placental OCTN2 expression and the underlying mechanisms in human choriocarcinoma BeWo cells. In addition, OCTN2 expression was measured in human placentas isolated from pregnancy with or without preeclampsia. After treatment of troglitazone, rosiglitazone and pioglitazone in BeWo cells, the mRNA and protein levels were analyzed by RT-qPCR and Western blotting, respectively. The results showed that, after 72 hr of treatment with troglitazone (10 μM), OCTN2 mRNA expression was significantly reduced by 60% in BeWo cells. In contrast, rosiglitazone (10 μM) and pioglitazone (10 μM) did not cause any change in OCTN2 mRNA expression in BeWo cells. Results of OCTN2 protein expression were consistent with those in mRNA. Troglitazone treatment significantly reduced both PPARα and RXRα mRNA levels. In contrast, treatment with rosiglitazone or pioglitazone did not reduce PPARα or RXRα mRNA expression. Both mRNA and protein levels of HIF-1α were increased by troglitazone treatment in BeWo cells, along with an increase in p38 activity and a decrease in Erk activity. In addition, the expression of OCTN2 and PPARα protein was significantly reduced in human placenta explants by hypoxia treatment and in placentas isolated from preeclampsia. In conclusion, troglitazone, but not rosiglitazone or pioglitazone, regulates OCTN2 and HIF-1α expression in placental choriocarcinoma BeWo cells and this effect may be mediated by mitogen-activated protein kinase. Hypoxia treatment caused a decrease in OCTN2 and PPARα expression in human placenta explants, which resembles the findings in preeclamptic placentas.