Valproic acid promotes neurite outgrowth in PC12 cells independent from regulation of the survival of motoneuron protein.
Spinal muscular atrophy (SMA) is a neurodegenerative disorder of motoneurons. The disease is caused by deletions or mutations of the survival of motoneuron gene 1 (SMN1). The amount of protein expressed from the second gene, SMN2, correlated with the severity of the clinical phenotype. The histone deacetylase inhibitor valproic acid (VPA) has been shown to increase the total cellular amount of functional SMN protein and is therefore considered as a drug candidate for treatment of SMA. In this study, we analyzed the effects of VPA in PC12 cells, a model system for neuronal differentiation, with regard to neurite outgrowth and SMN expression. VPA promoted neurite outgrowth in PC12 cells. However, this effect did not correlate with upregulation of SMN protein levels, suggesting a SMN-independent mechanism for VPA regulation of neurite outgrowth.
van Bergeijk
Jeroen
J
Department of Neuroanatomy, Hannover Medical School, OE 4140, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Haastert
Kirsten
K
Grothe
Claudia
C
Claus
Peter
P
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049108:Cell Enlargement / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis* / Q000502:physiology; D009134:Muscular Atrophy, Spinal / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016716:PC12 Cells; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D051381:Rats; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D015854:Up-Regulation / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; D014635:Valproic Acid