The Neuronal Apoptosis Inhibitory Protein (NAIP) is neuroprotective in several disease and trauma models. Therapy based on NAIP's upregulation might be possible with a detailed understanding of its expression in neurons. Sodium butyrate (NaB), a Naip upregulating compound, was used to investigate its transcriptional regulation. Preliminary studies suggested that Naip upregulation was a result of NaB's G protein coupled receptor (GPCR) mediated signaling pathway activation. Kinase and receptor

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... hibition experiments in the present study revealed no specific pathway responsible and confirmed that NaB mediated Naip induction is GPCR-independent. This is consistent with NaB's histone deacetylase inhibitor (HDACi) capacity underlying Naip induction, and supported by induction of Naip using another potent HDACi, Trichostatin A. We demonstrate that Naip induction following HDACi treatment is concomitant with G 1/G0 cell cycle arrest, p21 induction and E2f1 downregulation, suggesting a cell cycle associated regulation. Further examination revealed that p21 expression and cell cycle arrest are not required for HDACi mediated NAIP induction. Direct histone acetylation following HDACi treatment appears to be responsible for Naip induction.