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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.

Abstract
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-II-induced 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.
AuthorsJ C Hershey, M Hautmann, M M Thompson, L I Rothblum, T A Haystead, G K Owens
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 270 Issue 42 Pg. 25096-101 (Oct 20 1995) ISSN: 0021-9258 [Print] United States
PMID7559641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA-Binding Proteins
  • Pol1 Transcription Initiation Complex Proteins
  • RNA, Ribosomal, 18S
  • Transcription Factors
  • transcription factor UBF
  • Angiotensin II
  • Serine
  • Casein Kinase II
  • Protein Serine-Threonine Kinases
Topics
  • Angiotensin II (toxicity)
  • Animals
  • Casein Kinase II
  • Cells, Cultured
  • DNA-Binding Proteins (metabolism)
  • Hypertrophy
  • Muscle, Smooth, Vascular (drug effects, metabolism, pathology)
  • Phosphorylation
  • Pol1 Transcription Initiation Complex Proteins
  • Protein Serine-Threonine Kinases (metabolism)
  • RNA, Ribosomal, 18S (biosynthesis)
  • Rats
  • Serine (metabolism)
  • Transcription Factors (metabolism)
  • Transcription, Genetic (drug effects)

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