Tanshinone IIA regulates expression of glucose transporter 1 via activation of the HIF-1α signaling pathway

Tanshinone IIA (Tan 2A) is a lipid-soluble compound extracted from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It protects neuron and microvascular endothelial cells against hypoxia/ischemia both in vitro and in vivo however the mechanism is not fully known. Glucose transporter 1 (GLUT-1) is ubiquitously expressed in all types of tissue in the human body and serves important physiological functions due to its glucose uptake ability. The present study evaluated the role of Tan 2A in regulating GLUT-1 expression and its potential mechanism. RT-PCR and western Blot were used to detect the expression of GLUT-1. Si RNA mediated knockdown and CHIP assay were used to explore the mechanism of Tan 2A on GLUT-1expression. Tan 2A treatment induced expression of GLUT-1 and subsequently increased glucose uptake in endothelial cells (ECs). Furthermore, mRNA expression levels of vascular endothelial cell growth factor, BCL2 interacting protein 3 and enolase 2, which are target genes for hypoxia-inducible factor-1α (HIF-1α), were significantly upregulated by Tan 2A. Co-immunoprecipitation demonstrated that Tan 2A markedly increased the association of HIF-1α with recombination signal-binding protein for immunoglobulin κJ region (RBPJκ). Moreover, knockdown of HIF-1α and RBPJκ significantly reversed the regulatory effect of Tan 2A on mRNA expression levels of these genes in ECs. The results of the present study suggested that HIF-1α partially mediated the regulatory effect of Tan 2A on GLUT-1 expression in ECs. Therefore, GLUT-1 may be a potential therapeutic target for Tan 2A.