Tyrosine Hydroxylase Induction by Basic Fibroblast Growth Factor and Cyclic AMP Analogs in Striatal Neural Stem Cells: Role of ERK1/ERK2 Mitogen-activated Protein Kinase and Protein Kinase C

Abstract

S U M M A R YNeural stem cells (NSC) with self-renewal and multilineage potential are considered good candidates for cell replacement of damaged nervous tissue. In vitro experimental conditions can differentiate these cells into specific neuronal phenotypes. In the present study, we describe the combined effect of basic fibroblast growth factor (bFGF) and dibutyryladenosine 3 Ј ,5 Ј -cyclic monophosphate (dbcAMP) on the differentiation of fetal rat striatal NSC into tyrosine hydroxylase-positive cells. Tyrosine hydroxylase induction was accompanied by the activation of ERK1/ERK2 mitogen-activated protein kinase and was inhibited by the ERK1/ERK2 pathway blocker PD98059, suggesting that ERK activation may be important for this process. In addition, protein kinase C (PKC) was shown to be required for tyrosine hydroxylase protein expression. The inhibition of PKC by staurosporin, as well as its downregulation, decreased the ability of bFGF ϩ dbcAMP to generate tyrosine hydroxylase-positive cells. Moreover, the PKC activator phorbol 12-myristate 13-acetate (PMA) together with bFGF and dbcAMP led to a significant increase in phospho-ERK1/ERK2 levels, and the percentage of ␤ -tubulin III-positive cells that expressed tyrosine hydroxylase increased by 3.5-fold. PMA also promoted the phosphorylation of the cyclic AMP response element binding protein that might contribute to the increase in tyrosine hydroxylase-positive cells observed in bFGF ϩ dbcAMP ϩ PMA-treated cultures. From these results, we conclude that the manipulation in vitro of NSC from rat fetal striatum with bFGF, cyclic AMP analogs, and PKC activators promotes the generation of tyrosine hydroxylase-positive neurons.

Detoxified Extract of Rhus verniciflua Stokes Inhibits Rotenone-Induced Apoptosis in Human Dopaminergic Cells, SH-SY5Y

“…The expression of TH plays a crucial role in regulating the survival pathway induced by neurotrophins. Several studies have been reported that growth factors, neurotrophic factors, and bioactive peptides increases TH expression in cultured cells and tissues and supported the survival and differentiation of midbrain DA neurons (Nagatsu 1995;Theofilopoulos et al 2001;Lopez-Toledano et al 2004). In this study, we found that DRE suppressed the effects of rotenone on TH expression.…”

Intrastriatal Infusion of Liver Growth Factor Stimulates Dopamine Terminal Sprouting and Partially Restores Motor Function in 6-Hydroxydopamine-lesioned Rats

“…Neurotrophic factors are compounds that enhance the survival and differentiation of selected types of neurons and, therefore, are considered promising therapeutic agents for the treatment of neurodegenerative disorders characterized by selective degeneration of certain neuronal groups (Garcia de Yebenes and Mena 2000;Fernandez-Espejo 2004;Krieglstein 2004). In addition, they are also critical for the expansion and differentiation of neural progenitors, a new and promising tool in neuroregeneration (Palmer et al 1999;Reimers et al 2001;Bazan et al 2004;Lopez-Toledano et al 2004).…”

Kainic acid triggers oligodendrocyte precursor cell proliferation and neuronal differentiation from striatal neural stem cells

“…KA increases neurite length and cell size in neurons derived from striatal EGF-NSC. Cyclic AMP may influence the growth and differentiation of neurons in culture (Nakao, 1998;Hansen et al, 2000;Lopez-Toledano et al, 2004;Kim et al, 2005). In our cultures, 1 and 100 lM KA raised intracellular cyclic AMP levels 1.6-and 1.3-fold, respectively.…”