Transcriptional up-regulation of antioxidant genes by PPARI inhibits angiotensin II-induced premature senescence in vascular smooth muscle cells

• Published in: Biochemical and biophysical research communications 2011-03, Vol.406 (4), p.564-569
• Main Authors: Kim, Hyo Jung, Ham, Sun Ah, Paek, Kyung Shin, Hwang, Jung Seok, Jung, Si Young, Kim, Min Young, Jin, Hanna, Kang, Eun Sil, Woo, Im Sun, Kim, Hye Jung, Lee, Jae Heun, Chang, Ki Churl, Han, Chang Woo, Seo, Han Geuk
• Format: Article
• Language: English
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2011.02.091

This study evaluated peroxisome proliferator-activated receptor (PPAR) I as a potential target for therapeutic intervention in Ang II-induced senescence in human vascular smooth muscle cells (hVSMCs). Activation of PPARI by GW501516, a specific agonist of PPARI, significantly inhibited the Ang II-induced premature senescence of hVSMCs. Agonist-activated PPARI suppressed the generation of Ang II-triggered reactive oxygen species (ROS) with a concomitant reduction in DNA damage. Notably, GW501516 up-regulated the expression of antioxidant genes, such as glutathione peroxidase 1, thioredoxin 1, manganese superoxide dismutase and heme oxygenase 1. siRNA-mediated down-regulation of these antioxidant genes almost completely abolished the effects of GW501516 on ROS production and premature senescence in hVSMCs treated with Ang II. Taken together, the enhanced transcription of antioxidant genes is responsible for the PPARI-mediated inhibition of premature senescence through sequestration of ROS in hVSMCs treated with Ang II.