Hypernuclear acetylation in atherosclerotic lesions and activated vascular smooth muscle cells.
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.
Kawahara
K
K
Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
Watanabe
S
S
Ohshima
T
T
Soejima
Y
Y
Oishi
T
T
Aratani
S
S
Nakata
M
M
Shibata
M
M
Inoue
K
K
Amano
T
T
Fujii
R
R
Yanai
K
K
Hagiwara
M
M
Fukamizu
A
A
Maruyama
I
I
Nakajima
T
T
D000107:Acetylation / Q000187:drug effects; D000906:Antibodies / Q000276:immunology; D002070:Butadienes / Q000494:pharmacology; D050882:CREB-Binding Protein; D002102:Cadaver; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection
D000906:Antibodies; D002070:Butadienes; D004791:Enzyme Inhibitors; D006388:Hemagglutinins; D009570:Nitriles; D009687:Nuclear Proteins; D015534:Trans-Activators; C113580:U 0126; C002315:N(alpha)-acetyllysine; C016949:N-epsilon-acetyllysine; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin; D008239:Lysine