Aluminum-maltolate induces apoptosis and necrosis in neuro-2a cells: Potential role for p53 signaling

Aluminum maltolate (Al-malt) causes neurodegeneration following in vivo exposure, and apoptosis plays a prominent role. The objective of this study was to define the form of cell death induced by Al-malt and to establish an in vitromodel system amen-able to mechanistic investigations of Al-malt-induced cell death. Neuro-2a cells, a murine neuroblastoma cell line, were treated withAl-malt for 24 h, followingwhichmode of cell death and altera-tions in apoptosis-related gene expression were studied. Al-malt concentration-dependently increased cell death. The mode of cell death was a combination of apoptosis and necrosis. Treatment with Al-malt resulted in caspase 3 activation and the externalization of phosphatidyl serine, both indicative of apoptosis. In addition, nuclear condensation and fragmentation were evident. Interest-ingly, pretreatment with cycloheximide (CHX), a potent protein synthesis inhibitor markedly reduced Al-malt-induced apoptosis