ANG II- or AVP-induced increases in protein synthesis are not dependent on autocrine secretion of PDGF-AA

Stouffer, George A.; Shimizu, R. T.; Turla, Mila B.; Owens, Gary K.

doi:10.1152/ajpcell.1993.264.2.c390

Cited by 23 publications

(9 citation statements)

References 23 publications

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Section: Hypertrophy Of Vascular Smooth Muscle Cells (Vsmc)mentioning

confidence: 82%

“…In general, however, A-II has been shown to have a very low efficacy as a mitogen for cultured VSMC, and in cases where A-II is mitogenic, its proliferative effects seem to be mediated by autocrine factors such as platelet-derived growth factor-AA, transforming growth factor-␤, and/or b-fibroblast growth factor (15-17). In contrast, the A-II-induced hypertrophy of VSMC appears to be direct (12,18).There has been considerable interest in identifying the mechanism and cellular signaling pathways whereby A-II stimulates VSMC hypertrophy. One approach has been to attempt to identify which of the many signal transduction pathways stimulated by A-II (e.g.…”

mentioning

confidence: 99%

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Angiotensin II-induced Hypertrophy of Rat Vascular Smooth Muscle Is Associated with Increased 18 S rRNA Synthesis and Phosphorylation of the rRNA Transcription Factor, Upstream Binding Factor

Hershey

Hautmann

Thompson

et al. 1995

Journal of Biological Chemistry

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Hypertrophy of vascular smooth muscle cells (VSMC)is an important adaptive response of hypertension. Drug intervention studies have implicated a role for angiotensin II (A-II) in the mediation of VSMC hypertrophy in vivo, and A-II is a potent hypertrophic agent for VSMC in culture. Our laboratory has previously shown that A-II-induced hypertrophy of cultured VSMC is due in part to generalized increases in protein synthesis and increased content of rRNA. The aim of the present study was to determine if A-II stimulates rRNA gene synthesis and whether the rRNA transcription factor, upstream binding factor (UBF), is involved. Nuclear run-on analysis demonstrated that A-II induced a greater than 5-fold increase in rRNA gene synthesis within 6 h of stimulation. A-II also stimulated a rapid increase in UBF phosphorylation as well as nucleolar localization, but no changes in the content of UBF. Phosphoamino acid analysis showed that phosphorylation occurred only on serine residue(s). Results demonstrate that increased transcription of ribosomal DNA contributes to the A-IIinduced increase in protein synthesis and VSMC hypertrophy, and suggest that an important regulatory event in this pathway may be the phosphorylation and/or nucleolar localization of UBF.It is well established that arteries from hypertensive patients (1, 2) and animals (3, 4) are thicker than those from their normotensive counterparts. The arterial medial thickening is believed to represent an important adaptive response to normalize the elevated wall stress that occurs secondary to the increased blood pressure (3). Previous studies in this and other laboratories have demonstrated that medial thickening, at least in large conduit vessels, is due in part to increased vascular smooth muscle cell (VSMC) 1 content or mass, which occurs primarily by enlargement or hypertrophy of preexisting VSMC, with little to no change in VSMC number (5-7). As such, there has been considerable interest in identifying cellular mechanisms that mediate hypertrophic growth of vascular smooth muscle. There is clear evidence implicating a role for angiotensin II (A-II) in mediation of VSMC hypertrophy during chronic hypertension (8). For example, angiotensin-converting enzyme inhibitors and A-II receptor antagonists have been shown to be extremely effective in inhibiting development of VSMC medial hypertrophy in a variety of hypertensive animal models (9 -11). Importantly, effects of angiotensin-converting enzyme inhibitors or A-II antagonists do not appear to be due simply to blood pressure lowering, since other antihypertensive drugs were not as efficacious in blocking hypertrophy despite similar reductions in blood pressure. Consistent with in vivo studies, several laboratories, including our own, have shown that A-II stimulates increased protein synthesis and cellular hypertrophy in cultured VSMC via stimulation of angiotensin AT 1 receptors (12, 13). The mechanism of this effect is not clear. Moreover, our understanding in this area has been confounded by observations impli...

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Section: Hypertrophy Of Vascular Smooth Muscle Cells (Vsmc)mentioning

confidence: 82%

mentioning

confidence: 99%

Angiotensin II-induced Hypertrophy of Rat Vascular Smooth Muscle Is Associated with Increased 18 S rRNA Synthesis and Phosphorylation of the rRNA Transcription Factor, Upstream Binding Factor

Hershey

Hautmann

Thompson

et al. 1995

Journal of Biological Chemistry

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“…2, A and B), the inducible complex (arrow) consistently formed in response to ATII. Interestingly, induction of this complex within 1 h precedes the earliest detection of inducible PDGF-A mRNA in SMCs exposed to ATII, which typically occurs within approximately 4 h (29,31,32). Further experiments determined that the complex formed in a dose-dependent manner at ATII concentrations as low as 10 Ϫ10 M (data not shown).…”

Section: Atii Induces the Specific Interaction Of Nuclear Proteins Wimentioning

confidence: 94%

“…Electrophoretic Mobility Shift Assay-Binding reactions for gel shift assays were performed in 20 l of 10 mM Tris-HCl, 50 mM MgCl 2 , 1 mM EDTA, 1 mM DTT, 5% glycerol, 1 mM PMSF, 1 g salmon sperm DNA, 5% sucrose, 1 g poly(dI-dC), 32 P-labeled oligonucleotide (150,000 cpm), and 2.5-3 g of nuclear extract. The reaction was incubated for 35 min at 22°C.…”

Section: Chemicals-atii Phorbol 12-myristate 13-acetate (Pma) (S)-mentioning

confidence: 99%

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Angiotensin II (ATII)-inducible Platelet-derived Growth Factor A-chain Gene Expression Is p42/44 Extracellular Signal-regulated Kinase-1/2 and Egr-1-dependent and Mediated via the ATII Type 1 but Not Type 2 Receptor

Day

Rafty

Chesterman

et al. 1999

Journal of Biological Chemistry

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Angiotensin II (ATII) and platelet-derived growth factor (PDGF) are two vasoconstrictors implicated in the maintenance of normal vascular homeostasis. PDGF Achain levels increase in cultured vascular smooth muscle cells (SMCs) exposed to ATII. The molecular mechanisms underlying this induction are not known. We used transient transfection analysis to show that ATII can increase reporter gene activity driven by fragments of the PDGF-A promoter bearing recognition elements for the transcription factor, Egr-1. Nuclear run-off experiments indicate that ATII induces Egr-1 expression at the level of transcription. Gel shift and supershift studies show that Egr-1 protein accumulates in the nuclei of SMCs exposed to ATII and binds to the proximal region of the PDGF-A promoter in a specific, time-dependent manner. ATII induced extracellular-signal regulated kinase (p42/44 ERK) activity as did phorbol 12-myristate 13-acetate. The specific MEK1/2 inhibitor, PD98059, suppressedbothPDGF-AandEgr-1endogenousandpromoter-dependent expression inducible by ATII. The ATII type 1 receptor (AT1) antagonist, Losartan, inhibited ATII-induction of p42/44 ERK, as well as Egr-1 and PDGF-A, whereas neither PD123319, an AT2 receptor antagonist, nor wortmannin, an inhibitor of phosphatidylinositol 3-kinase and c-Jun N-terminal kinase, had any effect. ATII-induction of Egr-1 and PDGF-A was blocked by SIN-1, a NO donor. In addition, this pathway was blocked by overexpression of NO synthase. Collectively, these findings demonstrate that ATII activation of the PDGF-A promoter is mediated via the MEK/ERK/Egr-1 pathway and AT1 receptor and that this process is antagonized by NO.Angiotensin II (ATII), 1 a peptide hormone with potent vasoconstrictor activity, has long been implicated in the pathobiology of hypertension. In vascular smooth muscle cells (SMCs), ATII stimulates protein synthesis (1), cellular hypertrophy (2-5), migration (6), extracellular matrix synthesis (7,8), and the activation of a large number of transcription factors. These include Jak/STAT (9), Ets-1 (10), SRF (11), MHox (11), c-Jun (12, 13), JunB (12), and c-Fos (14). ATII is produced in the vessel wall by the actions of renin, which converts angiotensinogen to ATI, which is then cleaved to ATII by angiotensin-converting enzyme. Two ATII receptor subtypes have been described, AT1 and AT2. Signal transduction through G-protein-coupled AT1 receptors involves phospholipase C, phospholipase A 2 , phospholipase D, adenylate cyclase, and the release of intracellular calcium (reviewed in Refs. 15 and 16). The AT1 receptor also regulates neointimal thickening after mechanical injury to the rat carotid artery wall and ATII infusion (17). AT2 receptor signaling is less well understood, but evidence suggests that this receptor is involved in growth inhibition (18), Bcl-2 dephosphorylation (19), and apoptosis (20, 21). Platelet-derived growth factor (PDGF) consists of an A-chain and B-chain held together in homo-or heterodimeric configuration by disulfide bonds (reviewed in Refs. 22 and 2...

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Determinants of angiotensin II‐induced hypertrophy versus hyperplasia in vascular smooth muscle

Owens

1993

Drug Development Research

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ANG II- or AVP-induced increases in protein synthesis are not dependent on autocrine secretion of PDGF-AA

Cited by 23 publications

References 23 publications

Angiotensin II-induced Hypertrophy of Rat Vascular Smooth Muscle Is Associated with Increased 18 S rRNA Synthesis and Phosphorylation of the rRNA Transcription Factor, Upstream Binding Factor

Angiotensin II-induced Hypertrophy of Rat Vascular Smooth Muscle Is Associated with Increased 18 S rRNA Synthesis and Phosphorylation of the rRNA Transcription Factor, Upstream Binding Factor

Angiotensin II (ATII)-inducible Platelet-derived Growth Factor A-chain Gene Expression Is p42/44 Extracellular Signal-regulated Kinase-1/2 and Egr-1-dependent and Mediated via the ATII Type 1 but Not Type 2 Receptor

Determinants of angiotensin II‐induced hypertrophy versus hyperplasia in vascular smooth muscle

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