Regulation of Tyrosine Hydroxylase Gene Expression in IMR‐32 Neuroblastoma Cells by Basic Fibroblast Growth Factor and Ciliary Neurotrophic Factor

Abstract

The actions of basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) on tyrosine hydroxylase (TH) gene expression were studied using IMR‐32 neuroblastoma cells. Treatment of these cells with bFGF for 3 days induced the expression of detectable levels of immunoreactive TH protein and TH mRNA. In contrast, CNTF did not affect TH expression unless bFGF was present. In the presence of saturating amounts of bFGF, CNTF increased TH protein and mRNA levels of TH two‐ to threefold over those found in bFGF‐treated cultures. The effects of CNTF on TH expression diminished with increasing culture time, and after 6 days of incubation CNTF no longer enhanced TH levels. The requirement for bFGF as cofactor in the effects of CNTF on TH was specific, as CNTF did not affect TH when it was coadministered with 8‐(4‐chlorophenylthio)‐cyclic AMP, another agent that stimulates TH development in this cell line, and bFGF was not required for CNTF to stimulate the development of choline acetyltransferase. Moreover, cotreatment with bFGF reduced the ability of CNTF to enhance choline acetyltransferase. These results demonstrate that bFGF and CNTF can enhance expression of TH and that bFGF can modify the effects of CNTF on neurotransmitter phenotype.

Effects of defective herpes simplex vectors expressing neurotrophic factors on the proliferation and differentiation of nervous cells in vivo

“…It should be noted that these data relate either to peripheral preparations 26 or to CNS in vitro cell systems. 8,18,[21][22][23][24][25]27 Thus, the present one is the first evidence of a synergy between FGF-2 and CNTF occurring in the CNS in vivo.…”

“…These data support the notion that these two NTFs, when acting together, promote proliferation and glial differentiation. 8,18,21 However, depending on the experimental conditions, the developmental stage and the nervous system region, oligodendroglial 24,26 and neuronal 22,23,25,27 differentiation have also been reported. It should be noted that these data relate either to peripheral preparations 26 or to CNS in vitro cell systems.…”

“…8,18,21 Under specific experimental conditions, however, the combination of FGF-2 and CNTF has also been reported to promote oligodendroglial or neuronal differentiation. [22][23][24][25][26][27] Thus, it was expected that vectors expressing FGF-2 and CNTF would mimic this effect both in vitro and in the adult brain. Indeed, this proved to be the case.…”

12‐O‐tetradecanoyl‐phorbol‐13‐acetate‐dependent up‐regulation of dopaminergic gene expression requires Ras and neurofibromin in human IMR‐32 neuroblastoma

“…We now provide evidence that TPA‐induced TH transcription also requires neurofibromin and Ras. Although we did not evaluate TH enzymatic activity in these studies, it is reasonable to expect that it will also proportionally reflect the increases in TH protein and/or mRNA levels, as established in numerous previous studies on neuroblastoma cells, primary neurones and brain slices (Rabinovsky et al . 1995; Ma et al .…”

Protein Kinase C Activators Work in Synergy with Specific Growth Factors to Initiate Tyrosine Hydroxylase Expression in Striatal Neurons in Culture

“…neurons by growth factor and partner molecules are not yet well understood. However, in cells where the TH gene is constitutively expressed (e.g., PCI2 cells or adrenal chromaffin cells), stimulation of protein kinases, such as protein kinase A (PKA) Kim et al, 1993aKim et al, ,b, 1994 and protein kinase C (PKC) (Vyas et a!., 1990;Icard-Liepka!ns et al, 1992), growth factors (McTigue et al, 1985;GizangGinsberg andZiff, 1990, 1994;Rabinovsky et al, 1992Rabinovsky et al, , 1995Puchacz et al, 1993), and other stimuli (Lewis et a!., 1983Faucon Biguet et a!., 1991) are believed to be involved in the up-regulation of TH transcription.…”