(Hypertension. 1996;27:1224-1233.)
© 1996 American Heart Association, Inc.
Articles |
Multiple Enhancer Elements Mediate Induction of c-fos in Vascular Smooth Muscle Cells
From the Department of Medicine, Division of Cardiology (Y.-Q.C., D.M.G., B.R.), and Department of Pharmacology (A.J.N.), Vanderbilt University, Nashville, Tenn.
Correspondence to Allen J. Naftilan, MD, PhD, Department of Medicine, Division of Cardiology, Room 315 MRB II, Vanderbilt University, Nashville, TN 37232-2170. E-mail naftila@macpost.vanderbilt.edu.
Abstract Previous work from this and other laboratories has demonstrated that the vasoconstrictor peptide angiotensin II results in hypertrophy of rat aortic smooth muscle cells that is associated with an increase in transcription of the early growth response gene c-fos. To explore the molecular mechanism responsible for c-fos induction in rat aortic smooth muscle cells, we used a series of reporter constructs linked to the chloramphenicol acetyl transferase gene in transient transfection experiments in rat aortic smooth muscle cells. Constructs containing both the serum response element and cAMP response element exhibited a 20-fold increase in chloramphenicol acetyl transferase activity in response to either serum or angiotensin II, whereas no increase was seen in vehicle-treated cells. Mutations in either the serum response element or cAMP response element alone, which have been demonstrated to inactivate these elements in other cell types, had no effect on chloramphenicol acetyl transferase inducibility. In contrast, if both elements were mutated, inducibility was almost abolished. Electrophoretic mobility shift assays with oligonucleotides corresponding to either serum response element or cAMP response element demonstrated that these oligonucleotides are capable of forming specific complexes with proteins from rat aortic smooth muscle cell nuclear extracts. One of the proteins binding to the serum response element is the previously described serum response factor, since it was supershifted by a monospecific antibody. These studies demonstrate that c-fos induction in smooth muscle occurs by a dual mechanism that can activate transcription via the serum response element or cAMP response element. These elements appear to act equally and independently, involving a distinct set of transacting factors.
Key Words: angiotensin II • c-fos • muscle, smooth, vascular • genetics
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