Effects of taurine on glutamate uptake and degradation in Muller cells under diabetic conditions via antioxidant mechanism

Glutamate is the excitatory neurotransmitter in the retina, but it is neurotoxic in excessive amounts. A decrease in the ability of Muller cells to remove glutamate from the extracellular space may play a crucial role in the disruption of glutamate homeostasis that occurs in the diabetic retina. Previously we have shown that taurine has protective effects against diabetes-induced glutamate dysmetabolism in retinal Muller cells. The aim of this study is to examine the effects and underlying mechanism of taurine on high glucose-induced alterations of Muller cells glutamate uptake and degradation. Muller cells cultures were prepared from 5- to 7-day-old Sprague-Dawley rats. Glutamate uptake was measured as H-3-glutamate content of the lysates. Glutamine synthetase (GS) activity was assessed by a spectrophotometric assay. The expressions of glutamate transporters (GLAST) and GS were examined by RT-PCR and western-blot. In 25 mmol/l high glucose-treated cultures, Muller cells glutamate uptake, GS activity and GLAST, GS expressions were decreased significantly compared with 5 mmol/l normal glucose cultures (p< 0.05). Taurine (1 and 10 mmol/l) significantly inhibited the high glucose-induced decreases in glutamate uptake, GS activity and GLAST, GS expressions ( p <0.05). The generation of TBARS, ROS and NO in Muller cells increased significantly after treatment with high glucose compared with normal glucose. However, treatment of 1 and 10 mmol/l taurine resulted in a significant decrease in TBARS, ROS and NO levels ( p< 0.05). The high glucose treatment decreased antioxidant enzyme (catalase, SOD and GSH-px) activities compared with normal glucose. Taurine treatment increased the catalase, SOD and GSH-px activity in a dose-dependent manner. These findings suggest that taurine may regulate Muller cells' glutamate uptake and degradation under diabetic conditions via its antioxidant mechanism. (C) 2010 Elsevier Inc. All rights reserved.