Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Histone deacetylase (HDAC) inhibitors can induce neuronal differentiation. The effect of HDAC inhibitors is not limited to neuronal differentiation but to cell survival. We have reported that treatment with HDAC inhibitors promotes neurite outgrowth and cell survival via expression of nerve growth factor IB (Nur77), one of the immediate early genes (IEG), in rat PC12 cells. While Nur77 leads to expression of a family of proteins, including Nor1, the function of Nor1 following HDAC inhibitor treatment remains unclear. Thus, we analyzed whether Nor1 is an essential gene product for neurite out growth in response to HDAC inhibitors, compared with the expression of Nur77 in response to forskolin (FSK), because FSK is known to induce neurite outgrowth. We used HDAC inhibitors (trichostatin A (TSA) or K-350) and FSK as a positive control for neurite outgrowth. We also added siRNA to deplete the expression of Nur77. The neurites were photographed using phase-contrast microscopy and the length of each neurite was measured using analysis software. We found that TSA and K-350 both induced neurite outgrowth accompanied with expression of Nur77 after treatment of the cells for 24 hours. We also observed that only FSK induced the expression of Nor1. Furthermore, siRNA against mRNA for Nur77 prevented the TSA-induced neurite outgrowth. These results suggest that while the expression of Nor1 is not essential, the expression of Nur77 is necessary for neurite outgrowth by HDAC inhibitors.

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