p53 Inactivation leads to enhancement of tyrosine hydroxylase biosynthesis in brain dopaminergic neurons

In this paper we address a possibility of interaction among protein 53, members of the ERK1/2 signaling pathway, and the CREB transcription factor in regulation of activity of dopaminergic neurons. Nerve cells in the substantia nigra and zona incerta have been studied in control rats and in rats with pifithrin-alpha, a transcriptional inhibitor of p53, administered intraperitoneally. We have shown that p53 inhibition leads to an increased tyrosine hydroxylase content both in cell bodies and axon terminals. The CREB transcription factor activity is also enhanced in brain dopaminergic neurons. However, there have been observed no significant differences in phospho-ERK1/2 kinase content between cell bodies from pifithrin-alpha injected group and the control. It has been shown therefore that p53 exerts an inhibitory effect on tyrosine hydroxylase biosynthesis which may be mediated by the CREB.