Exendin-4 increases extracellular superoxide dismutase expression in cultured astrocytes

Under some pathological conditions in brain, a large amount of superoxide anion (O 2 -) is produced, causing various cellular damages.Among three isozymes of superoxide dismutase (SOD), extracellular (EC)-SOD should play a role to detoxify O 2 -in extracellular space; however, a little is known about EC-SOD in brain.Exendin 4 (Ex-4), an analogue of glucagon-like peptide-1 (GLP-1), binds to GLP-1 receptor to potentiate insulin secretion in pancreatic β cells and is used extensively as a drug for type 2 diabetes mellitus.It was reported that Ex-4 might represent neuroprotective effects; however, the details of mechanisms and the effects on glial cells were unclear.In the present study, we examined the effects of Ex-4 on EC-SOD expression in cultured rat cortical astrocytes.By means of RT-PCR, EC-SOD mRNA was increased by Ex-4 exposure in a time-dependent manner.The expression of EC-SOD protein was also increased by Ex-4 exposure for 24 h dose-dependently, and exendin (9-39), an antagonist of GLP-1 receptor, inhibited Ex-4-increased EC-SOD protein expression.Moreover, the cell-surface SOD activity in astrocytes and the activity of SOD released in the medium were not significantly affected by incubation of Ex-4 and/or exendin (9-39) for 24 h.These results suggest that Ex-4 might increase EC-SOD expression via binding to GLP-1 receptor although EC-SOD activities in astrocytes and in the medium were not affected.The regulation of EC-SOD in astrocytes may contribute to the defensive mechanism against oxidative stress in brain.