SIRT1 regulates tyrosine hydroxylase expression and differentiation of neuroblastoma cells via FOXO3a.
FEBS Lett. 2009 Mar 12;
Authors: Kim MJ, Ahn K, Park SH, Kang HJ, Jang BG, Oh SJ, Oh SM, Jeong YJ, Heo JI, Suh JG, Lim SS, Ko YJ, Huh SO, Kim SC, Park JB, Kim J, Kim JI, Jo SA, Lee JY
To examine the function of SIRT1 in neuronal differentiation, we employed all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. Nicotinamide inhibited neurite outgrowth and tyrosine hydroxylase (TH) expression. Inhibition of PARP or histone deacetylase did not inhibit TH expression, showing the effect to be SIRT1 specific. Expression of FOXO3a and its target proteins were increased during the differentiation and reduced by nicotinamide. FOXO3a deacetylation was increased by ATRA and blocked by nicotinamide. SIRT1 and FOXO3a siRNA inhibited ATRA-induced up-regulation of TH and differentiation. Taken together, these results indicate that SIRT1 is involved in ATRA-induced differentiation of neuroblastoma cells via FOXO3a.
PMID: 19285077 [PubMed - as supplied by publisher]