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Roscovitine Inhibits ERK1/2 Activation Induced by Angiotensin
Author(s) -
Wen Jinkun,
Li Aiying,
Han Mei
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.965.13
Subject(s) - vascular smooth muscle , angiotensin ii , phosphorylation , chemistry , apoptosis , restenosis , microbiology and biotechnology , medicine , endocrinology , pharmacology , biology , receptor , smooth muscle , biochemistry , stent
R‐Roscovitine (CYC202) is often as a biological tool in cell cycle and apoptosis studies. Our recent study showed that roscovitine significantly inhibited VSMC proliferation stimulated by angiotensin II (Ang II) or fetal bovine serum (FBS). However, the mechanism of action and the real targets of roscovitine in vascular smooth muscle cells (VSMCs) remain nuclear. To elucidate the molecular mechanism of action of roscovitine in VSMCs, in the present study, VSMCs were isolated from the thoracic aortas of male Sprague‐Dawley rats and treated with Ang II after pretreating VSMCs with roscovitine for 15 h. We found that ERK1/2 phosphorylation induced by Ang II is abrogated by pretreating VSMCs with roscovitine for 15 h. Pretreating VSMCs with roscovitine also inhibits Ang II‐induced c‐Jun expression and phosphorylation, leading to negative regulation of downstream gene angiotensinogen gene. Our data provided a possible molecular mechanism whereby the inhibitive effect of roscovitine on VSMC proliferation is mediated. This study provided the first evidence that roscovitine could inhibit ERK1/2 phosphorylation and block the c‐Jun induction and activation, consequentially inhibiting Ang II‐induced its precursor gene expression. The results give an evidence that roscovitine may be feasible and effective in treating cardiovascular diseases such as atherosclerosis and restenosis.