Mutated Recombinant Human Glucagon-like Peptide-1 Protects SH-SY5Y Cells from Apoptosis Induced by Glutamate

OBJECTIVE To investigate the effects of mutated recombinant human glucagon-like peptide-1(mGLP-1) on glutamate-induced SH-SY5Y cell apoptosis. METHODS A cyclic adenosine monophosphate (cAMP) kit was selected for assaying intracellular cAMP content. MTT assay was applied to detect the viability of SH-SY5Y cells exposed to glutamate or /and mGLP-1. Lactate dehydrogenase (LDH) release was measured to detect glutamate-induced cytotoxicity. Apoptosis morphological identification was evaluated with 4', 6-diamidino-2-phenylindole (DAPI) nuclear staining. The cytosolic calcium concentration was tested by calcium influx assay. The oxidative damage was estimated by measuring the malondialdehyde (MDA) content, superoxide dismutase (SOD) activity and total glutathione (total GS) level. RESULTS mGLP-1 could induce the increase of intracellular cAMP content. Glutamate cytotoxicity presented that low cell viability, high LDH release and increased cell apoptosis. After treatment with mGLP-1, glutamate-induced toxicity would be partially relieved. It was evident that mGLP-1 could decrease MDA content, increase SOD activity and total GS level, but could not change calcium concentration. CONCLUSION These data indicate that mGLP-1 has protective effects on glutamate-induced SH-SY5Y cell apoptosis through rescuing oxidative damage. It is suggested that mGLP-1 may have better potential therapeutic value in the treatment of neurodegenerative diseases since mGLP-1 presents a longer half-life than natural GLP-1.