Abstract
In present study, we investigated the role of hypoxia inducible factor-1 (HIF-1) in regulation of taurine transport through the blood-brain barrier (BBB) under high glucose condition using TR-BBB cells as an in vitro model of BBB. Treatment with high glucose (25 mM) for 48 h induced HIF-1α and VEGF expression, and decreased [3H]taurine uptake in TR-BBB cells. Also, high glucose condition reduced taurine transporter (TauT) mRNA and protein levels. In addition, pre-treatment with HIF-1 inducer, cobalt chloride in TR-BBB cells decreased TAUT expression. Glucose-induced TauT down-regulation could be reversed by inhibition of HIF-1 and VEGF using several HIF-1 and VEGF inhibitors. Also, both HIF-1 inhibitors and VEGF inhibitors induced the decrease of [3H]taurine uptake caused by high glucose. In conclusion, taurine transport through the BBB can be down-regulated by high glucose, which is mediated to induction of HIF-1 and VEGF. Therefore, we suggest that the inhibitors of HIF-1 and VEGF could have the beneficial effects on hyperglycemia by up-regulation of taurine contents in brain.
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