Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha. Export

@article{citeulike:5095975, abstract = {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.}, author = {Borniquel, Sara and Valle, Inmaculada and Cadenas, Susana and Lamas, Santiago and Monsalve, Mar\'{i}a}, citeulike-article-id = {5095975}, citeulike-linkout-0 = {http://dx.doi.org/10.1096/fj.05-5189fje}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16891621}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16891621}, doi = {10.1096/fj.05-5189fje}, issn = {1530-6860}, journal = {The FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, month = {September}, number = {11}, pages = {1889--1891}, posted-at = {2009-07-09 14:18:02}, priority = {3}, title = {Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha.}, url = {http://dx.doi.org/10.1096/fj.05-5189fje}, volume = {20}, year = {2006} }

TY - JOUR ID - citeulike:5095975 L3 - citeulike-article-id:5095975 N2 - 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. IS - 11 JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology SN - 1530-6860 EP - 1891 TI - Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha. VL - 20 SP - 1889 AU - Borniquel, Sara AU - Valle, Inmaculada AU - Cadenas, Susana AU - Lamas, Santiago AU - Monsalve, María PY - 2006/09// UR - http://dx.doi.org/10.1096/fj.05-5189fje ER -