Nicotinamide prevents apoptosis in human cortical neuronal cells.

In previous studies, the free radical generating toxin tertiary butylhydroperoxide (t-BuOOH) was found to induce significant cell death in human cortical neuronal cells (HCN2 cells). Pretreatment with the poly (ADP-ribose) polymerase (PARP) inhibitor nicotinamide was able to prevent HCN2 cell death. In this study it is observed that apoptosis is induced following the addition of t-BuOOH at 6 h as indicated by TUNEL-positive cells. When nicotinamide is added prior to t-BuOOH, it is able to prevent neuronal cell death and inhibit apoptosis. DNA microarray studies demonstrate that t-BuOOH administration causes an upregulation of proapoptotic genes like ICH-2 and BimL. On the other hand, nicotinamide-pretreated neurons have higher expression levels of inhibitors of apoptosis (IAP) genes. Therefore, it appears that one mechanism by which nicotinamide acts as neuroprotective agents is by elevating the gene expression levels of IAPs. Moreover, there is an upregulation of the glyceraldehydes-3-phosphate dehydrogenase gene in nicotinamide-pretreated HCN2 cells. Nicotinamide-pretreated cells also had higher expression levels of putative "death domain" genes like p75TNFR, TRAIL2, TNFR1, and HVEM-L. Thus, nicotinamide can regulate multiple apoptotic genes with seemingly opposite roles and through its action on these various genes prevent apoptosis of neuronal cells.