TY - JOUR T1 - Role for Early Growth Response-1 Protein in α<sub>1</sub>-Adrenergic Stimulation of Fibroblast Growth Factor-2 Promoter Activity in Cardiac Myocytes JF - Molecular Pharmacology JO - Mol Pharmacol SP - 984 LP - 990 VL - 57 IS - 5 AU - Yan Jin AU - Farah Sheikh AU - Karen A. Detillieux AU - Peter A. Cattini Y1 - 2000/05/01 UR - http://molpharm.aspetjournals.org/content/57/5/984.abstract N2 - Fibroblast growth factor-2 (FGF-2), a mitogenic, angiogenic, and cardioprotective agent, is released from the postnatal heart by a mechanism of transient remodelling of the sarcolemma during contraction. Both release of FGF-2 and its synthesis can be increased with adrenergic stimulation. We reported previously that FGF-2 synthesis can be regulated at the transcriptional level by α-adrenergic stimulation of cultured neonatal rat cardiac myocytes as well as in the adult mouse heart. Examination of the proximal promoter region of both human and rat FGF-2 gene sequences revealed binding sites for the early growth response-1 (Egr-1) protein. Using gel mobility shift assays, we observed a transient increase in a complex between nuclear extracts from neonatal rat cardiac myocytes treated with inducers of Egr-1, including the α-adrenergic agonist phenylephrine, angiotensin II, and phorbol ester, and a consensus Egr-1 DNA element. A similar complex was seen with the FGF-2 promoter region −7/+42 as the DNA probe, but not when the Egr-1 element at nucleotides +3/+31 was disrupted. Participation of Egr-1 protein in the complex was confirmed by competition with Egr-1 DNA elements and antibodies. With deletion analysis and transfection of neonatal rat cardiac myocytes, the α-adrenergic response was localized to nucleotides −110/+42 of the FGF-2 gene in the context of a hybrid FGF-2/luciferase reporter gene, −110FGFp.luc. Overexpression of Egr-1 increased −110FGFp.luc gene expression, whereas mutation of its Egr-1 element at nucleotides +3/+31 abolished α-adrenergic responsiveness. These data indicate that Egr-1 is involved in the α-adrenergic stimulation of the FGF-2 promoter region in neonatal cardiac myocytes. The American Society for Pharmacology and Experimental Therapeutics ER -