Crucial roles of MZF‐1 in the transcriptional regulation of apomorphine‐induced modulation of FGF‐2 expression in astrocytic cultures

Abstract

Apomorphine (APO), a potent D1/D2 dopamine receptor agonist, is used as an anti-parkinsonian drug. It stimulates the synthesis and release of multiple trophic factors in mesencephalic and striatal neurons, preventing the loss of dopaminergic neurons in vitro. Furthermore, APO enhances the biosynthesis and release of FGF-2 by activating dopamine receptors in striatal astrocytes, where cAMP/PKA and PKC/MAPK signalling cascades mediate this process. We investigate the effects of APO on the fibroblast growth factor-2 (FGF-2) promoter and its regulation in astrocytes and identify the transcription factor and cis element underlying these effects. In screening for cis-acting elements over the entire region of the FGF-2 promoter stimulated by APO in the astrocytes, a sequence located in the -785/-745 region was found to serve as the cis element. This element was recognized by the human myeloid zinc finger protein 1 (MZF-1) transcription factor. Introducing human MZF-1 plasmid and human MZF-1-specific siRNA has different effects on the FGF-2 promoter. Furthermore, it increases FGF-2 protein expression in HeLa cells and primary astrocytes, indicating that APO stimulates the FGF-2 promoter via the MZF-1 transcription factor. These data suggest that APO can enhance the biosynthesis and release of FGF-2 through the activation of the MZF-1 transcription factor in striatal astrocytes.