Sodium nitrite induces PC12 cell differentiation

To investigate the potential ability of the nitrite to induce neuronal differentiation of PC12 cells, cultured PC12 cells planted on matrigel in the presence or absence of sodium nitrite were employed as model, nerve growth factor (NGF) served as a positive control.  After 48 h, sodium nitrite enhanced cell viability and vascular endothelial growth factor (VEGF) secretion.  Same as the effect of NGF, sodium nitrite (1.4 mmol·L⁻¹) treated cultures contained a greater proportion of cells bearing neurites and neurites were much longer than those found in negative control cultures (P < 0.05).  Compared with the negative control, sodium nitrite (1.4 mmol·L⁻¹) also upregulated the expression of VEGF mRNA (P < 0.05) and hypoxia inducible factor 1α (HIF-1α) or VEGF protein expression (P < 0.05) in cultures of PC12 cells.  On the other hand, these effects of the sodium nitrite were likely mediated by HIF-1α, since their effects were antagonized by addition of HIF-1α inhibitor YC-1.  Taken together, these results suggest that low doses of sodium nitrite could induce neurite outgrowth in PC12 cells by activating the HIF-1α-VEGF pathway.