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SIRT1 regulates tyrosine hydroxylase expression and differentiation of neuroblastoma cells via FOXO3a |
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| Authors: | Min-Ju Kim Kyungsook Ahn Hong-Jun Kang Soo-Jin Oh Yu-Jin Jeong Jun-Gyo Suh Soon Sung Lim Yoon-Jung Ko Sung Chan Kim Jaebong Kim Sangmee Ahn Jo |
| Affiliation: | a Department of Biochemistry, College of Medicine, Hallym University, 1 Okchon-dong, Chuncheon, Gangwon-do 200-702, South Korea b Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea c Department of Pharmacology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea d Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea e Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea f Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea g Division of Brain Disease, Center for Biomedical Sciences, National Institute of Health, Seoul 122-701, South Korea h Department of Biochemistry, College of Medicine, Seoul National University, Seoul 100-799, South Korea |
| Abstract: | 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. |
| Keywords: | SIRT1 FOXO3a Nicotinamide Neuronal differentiation Neuroblastoma |
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