Small-interfering-RNA-mediated silencing of human glutamate dehydrogenase induces apoptosis in neuroblastoma cells

In the nervous system, GDH (glutamate dehydrogenase) is enriched in astrocytes and is important for recycling glutamate, a major excitatory neurotransmitter. The function of hGDH (human GDH) may be important in neurodegenerative diseases such as Parkinson's disease. To test the effect of decreased hGDH expression, several vector‐based plasmidlinked hGDH siRNAs (small interfering RNAs) were expressed intracellularly in BE(2)C human neuroblastoma cells. Immunoblotting and reverse‐transcription–PCR confirmed that expression of hGDH protein and mRNA was knocked down by co‐transfection with phGDH‐siRNA vectors in BE(2)C human neuroblastoma cells. TUNEL (terminal uridine deoxynucleotidyl transferase dUTP nick‐end labelling) and DNA fragmentation assays 48 h after transfection of phGDH‐siRNAs revealed that inhibition of hGDH expression induced cellular apoptosis and activated phospho‐ERK1/2 (phospho‐extracellular‐signal‐regulated kinase 1/2). These findings show that inhibition of hGDH expression by siRNA is related to apoptosis in neuronal cells.