Hypernuclear acetylation in atherosclerotic lesions and activated vascular smooth muscle cells

Biochem Biophys Res Commun. 1999 Dec 20;266(2):417-24. doi: 10.1006/bbrc.1999.1812.

Abstract

Recent studies have implicated acetylation of several nuclear proteins such as histones and p53 on their epsilon-portion of lysine residues in eukaryotic transcription. Here we raised a specific polyclonal antibody against epsilon-acetylated lysine. Using the antibody, we detected hypernuclear acetylation (HNA) in atherosclerotic vascular smooth muscle cells (VSMCs). Thrombin, a humoral factor known to cause activation and proliferation of VSMCs, strongly potentiated HNA in cultured VSMCs. MAP kinase pathway and a signal coactivator CREB binding protein (CBP) were involved in thrombin-induced HNA of VSMCs. Our results suggest that coactivators cooperating with signal-dependent transcription activators play an important role in atherosclerogenesis via HNA in VSMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Antibodies / immunology
  • Butadienes / pharmacology
  • CREB-Binding Protein
  • Cadaver
  • Cells, Cultured
  • Coronary Artery Disease / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Hemagglutinins / metabolism
  • Humans
  • Immunohistochemistry
  • Lysine / analogs & derivatives
  • Lysine / analysis
  • Lysine / immunology
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth, Vascular / metabolism*
  • Nitriles / pharmacology
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Thrombin / pharmacology
  • Trans-Activators / metabolism
  • Transfection

Substances

  • Antibodies
  • Butadienes
  • Enzyme Inhibitors
  • Hemagglutinins
  • Nitriles
  • Nuclear Proteins
  • Trans-Activators
  • U 0126
  • N(alpha)-acetyllysine
  • N-epsilon-acetyllysine
  • CREB-Binding Protein
  • CREBBP protein, human
  • Mitogen-Activated Protein Kinases
  • Thrombin
  • Lysine