Pulsatile equibiaxial stretch inhibits thrombin-induced RhoA and NF-κB activation
- 作者：Jason H. Haga ; Rol ; Kaunas ; Julie Radeff-Huang ; Jessica M. Weems ; Kristine D. Estrada ; Shu Chien ; Joan Heller Brown ; Tammy M. Seasholtz
- 关键词：Mechanical stretch ; RhoA ; Thrombin ; Vascular smooth muscle ; NF-κ ; B
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：18 July 2008
- 卷：372
- 期：1
- 页码：216-220
- 文件大小：450 K
摘要
This study investigated interactions between the effects of mechanical stretch and thrombin on RhoA activation in rat aortic smooth muscle cells (RASMC). Equibiaxial, pulsatile stretch, or thrombin produced a significant increase in RhoA activation. Surprisingly, in combination, 30 min of stretch inhibited the ability of thrombin to activate RhoA. NO donors and 8-bromo-cGMP significantly inhibited thrombin-induced RhoA activation. Interestingly, the nitric oxide synthase (NOS) inhibitor l-NAME increased basal RhoA activity, suggesting that NOS activity exerts a tonic inhibition on RhoA. Stretching RASMC increases nitrite production, consistent with the idea that NO contributes to the inhibitory effects of stretch. Thrombin stimulates MAP kinase and NF-κB pathways through Rho and these responses were blocked by 8-bromo-cGMP or stretch and restored by l-NAME. These data suggest that stretch, acting through NO and cGMP, can prevent the ability of thrombin to stimulate Rho signaling pathways that contribute to pathophysiological proliferative and inflammatory responses.