Activation of PPAR delta counteracts angiotensin II-induced ROS generation by inhibiting rac1 translocation in vascular smooth muscle cells

作者：Lee Hanna; Ham Sun Ah; Kim Min Young; Kim Jae Hwan; Paek Kyung Shin; Kang Eun Sil; Kim Hyo Jung; Hwang Jung Seok; Yoo Taesik; Park Chankyu; Kim Jin Hoi; Lim Dae Seog; Han Chang Woo; Seo Han Geuk^*

来源：Free Radical Research, 2012, 46(7): 912-919.

DOI：10.3109/10715762.2012.687448

• Angiotensin II
• NADPH oxidase
• peroxisome proliferator-activated receptor delta
• Rac1
• reactive oxygen species

Angiotensin II (Ang II)-mediated modification of the redox milieu of vascular smooth muscle cells (VSMCs) has been implicated in several pathophysiological processes, including cell proliferation, migration and differentiation. In this study, we demonstrate that the peroxisome proliferator-activated receptor (PPAR) delta counteracts Ang II-induced production of reactive oxygen species (ROS) in VSMCs. Activation of PPAR delta by GW501516, a specific ligand for PPAR delta, significantly reduced Ang II-induced ROS generation in VSMCs. This effect was, however, reversed in the presence of small interfering (si) RNA against PPAR delta. The marked increase in ROS levels induced by Ang II was also eliminated by the inhibition of phosphatidylinositol 3-kinase (PI3K) but not of protein kinase C, suggesting the involvement of the PI3K/Akt signalling pathway in this process. Accordingly, ablation of Akt with siRNA further enhanced the inhibitory effects of GW501516 in Ang II-induced superoxide production. Ligand-activated PPAR delta also blocked Ang II-induced translocation of Rac1 to the cell membrane, inhibiting the activation of NADPH oxidases and consequently ROS generation. These results indicate that ligand-activated PPAR delta plays an important role in the cellular response to oxidative stress by decreasing ROS generated by Ang II in vascular cells.

• 出版日期2012-7