Downregulation of the human taurine transporter by glucose in cultured retinal pigment epithelial cells

Downregulation of the human taurine transporter by glucose in cultured reti nal pigment epithelial cells. In diabetes, activation of the aldose reducta se (AR) pathway and alterations of glucose-sensitive signal transduction pa thways have been implicated in depletion of intracellular taurine, an endog enous antioxidant and compatible osmolyte. Cellular taurine accumulation oc curs by an osmotically induced, protein kinase C (PKC)-regulated Na+-taurin e cotransporter (hTT). The effects of ambient glucose on taurine content, h TT activity, and hTT gene expression were therefore evaluated in low and hi gh AR-expressing human retinal pigment epithelial cell lines. In low AR-exp ressing cells, 20 mM glucose decreased taurine content, hTT transporter act ivity, and mRNA levels, and these effects were unaffected by AR inhibition (ARI). In these cells, the inhibitory effects of high glucose on hTT appear ed to be posttranscriptionally mediated, because 20 mM glucose decreased hT T mRNA stability without affecting hTT transcriptional rate. Inhibition of PKC overcame the decrease in hTT activity in high glucose-exposed cells. In high AR-expressing cells, prolonged exposure to 20 mM glucose resulted in intracellular taurine depletion, which paralleled sorbitol accumulation and was prevented by ARI. In these cells exposed to 5 mM glucose, hTT mRNA abu ndance was decreased and declined further in 20 mM glucose but was correcte d by ARI. In 5 mM glucose, hTT transcriptional rate was markedly decreased in high AR-expressing cells, did not decline further in 20 mM glucose, but was increased by ARI to levels above those observed in low AR-expressing ce lls. Therefore, glucose rapidly and specifically decreases taurine content, hTT activity, and mRNA abundance by AR-unrelated and AR-related posttransc riptional and transcriptional mechanisms.