Reactive oxygen species-mediated homologous downregulation of angiotensin II type 1 receptor mRNA by angiotensin II

被引:25
作者
Ichiki, T [1 ]
Takeda, K [1 ]
Tokunou, T [1 ]
Funakoshi, Y [1 ]
Ito, K [1 ]
Iino, N [1 ]
Takeshita, A [1 ]
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, Fukuoka 8128582, Japan
关键词
receptor; angiotensin II; reactive oxygen species; protein kinases;
D O I
10.1161/01.HYP.37.2.535
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of angiotensin (Ang) II through Ang II type I receptor (AT(1)-R). However, the role of ROS in the regulation of AT(1)-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT(1)-R by Ang II. Ang II (10(-6) mol/L) decreased AT(1)-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells, Preincubation of vascular smooth muscle cells with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT(1)-R mRNA. The effect of NAC was due to stabilization of the AT(1)-R mRNA that was destabilized by Ang II. The Ang II-induced AT(1)-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as by PD98059. Exogenous H2O2 also suppressed AT(1)-R mRNA. These results suggest that the production of ROS and the activation of ERK an critical for the downregulation of AT(1)-R mRNA. The generation of ROS through stimulation of AT(1)-R not only mediates signaling of Ang II but also may play a crucial role in the adaptation process of AT(1)-R to the sustained stimulation of Ang II.
引用
收藏
页码:535 / 540
页数:6
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