| First Author | Borniquel S | Year | 2006 |
| Journal | FASEB J | Volume | 20 |
| Issue | 11 | Pages | 1889-91 |
| PubMed ID | 16891621 | Mgi Jnum | J:112736 |
| Mgi Id | MGI:3663242 | Doi | 10.1096/fj.05-5189fje |
| Citation | Borniquel S, et al. (2006) Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha. FASEB J 20(11):1889-91 |
| abstractText | Nitric oxide (NO) has both prooxidant and antioxidant activities in the endothelium; however, the molecular mechanisms involved are still a matter of controversy. PGC-1alpha [peroxisome proliferators-activated receptor (PPAR) gamma coactivator 1-alpha] induces the expression of several members of the mitochondrial reactive oxygen species (ROS) detoxification system. Here, we show that NO regulates this system through the modulation of PGC-1alpha expression. Short-term (<12 h) treatment of endothelial cells with NO donors down-regulates PGC-1alpha expression, whereas long-term (>24 h) treatment up-regulates it. Treatment with the NOS inhibitor l-NAME has the opposite effect. Down-regulation of PGC-1alpha by NO is mediated by protein kinase G (PKG). It is blocked by the soluble guanylate cyclase (sGC) inhibitor ODQ and the PKG inhibitor KT5823, and mimicked by the cGMP analog 8-Br-cGMP. Changes in PGC-1alpha expression are in all cases paralleled by corresponding variations in the mitochondrial ROS detoxification system. Cells that transiently overexpress PGC-1alpha from the cytomeglovirus (CMV) promoter respond poorly to NO donors. Analysis of tissues from eNOS(-/-) mice showed reduced levels of PGC-1alpha and the mitochondrial ROS detoxification system. These data suggest that NO can regulate the mitochondrial ROS detoxification system both positively and negatively through PGC-1alpha. |
