SIRT1 regulates tyrosine hydroxylase expression and differentiation of neuroblastoma cells via FOXO3a.
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.
Kim
Min-Ju
MJ
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea.
Ahn
Kyungsook
K
Park
Seong-Hoon
SH
Kang
Hong-Jun
HJ
Jang
Bong Geom
BG
Oh
Soo-Jin
SJ
Oh
Sun-Mee
SM
Jeong
Yu-Jin
YJ
Heo
Jee-In
JI
Suh
Jun-Gyo
JG
Lim
Soon Sung
SS
Ko
Yoon-Jung
YJ
Huh
Sung-Oh
SO
Kim
Sung Chan
SC
Park
Jae-Bong
JB
Kim
Jaebong
J
Kim
Jong-Il
JI
Jo
Sangmee Ahn
SA
Lee
Jae-Yong
JY
D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D024161:Collagen Type XI / Q000378:metabolism; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000494:pharmacology; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics; D014803:Vitamin B Complex / Q000494:pharmacology
D000970:Antineoplastic Agents; C499319:COL11A2 protein, human; D024161:Collagen Type XI; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D014803:Vitamin B Complex; D009536:Niacinamide; D014212:Tretinoin; D014446:Tyrosine 3-Monooxygenase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D006655:Histone Deacetylases