Bacqueville D, Casagrande F, Perret B, Chap H, Darbon J M, Breton-Douillon M
INSERM U 326, Toulouse, France.
Biochem Biophys Res Commun. 1998 Mar 27;244(3):630-6. doi: 10.1006/bbrc.1997.7885.
In the present study, we investigated the involvement of phosphatidylinositol 3-kinase (PI 3-kinase) activity in the progression of vascular smooth muscle cells (VSMCs) throughout the G1 phase of cell cycle. Addition of two selective inhibitors of PI 3-kinase, LY 294002 or wortmannin, to quiescent VSMCs prevented serum-induced DNA synthesis in a dose-dependent manner with IC50 of 8.7 +/- 2.0 microM and 53.9 +/- 8.5 nM, respectively. Time course studies revealed that the two PI 3-kinase inhibitors blocked VSMC proliferation in mid-late G1 phase, about 6 h before the G1/S transition. This G1 growth arrest was due, at least in part, to the reduction of the CDK2 associated kinase activity resulting mainly from the upregulation of the inhibitory protein p27KIP1.
在本研究中，我们调查了磷脂酰肌醇3激酶（PI 3激酶）活性在血管平滑肌细胞（VSMC）整个细胞周期G1期进程中的作用。向静止的VSMC中添加两种PI 3激酶选择性抑制剂LY 294002或渥曼青霉素，可剂量依赖性地抑制血清诱导的DNA合成，IC50分别为8.7±2.0微摩尔和53.9±8.5纳摩尔。时间进程研究表明，这两种PI 3激酶抑制剂在G1期中后期，即G1/S转换前约6小时，阻断了VSMC增殖。这种G1期生长停滞至少部分是由于抑制蛋白p27KIP1上调导致CDK2相关激酶活性降低所致。
