Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1α
| Autor: | Sara Borniquel, Inmaculada Valle, Susana Cadenas, Santiago Lamas, María Monsalve |
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| Přispěvatelé: | Ministerio de Educación y Ciencia (España), Centro Nacional de Investigaciones Cardiovasculares (España), Fundación Pro CNIC, Bancaja, Sociedad Española de Nefrología |
| Rok vydání: | 2006 |
| Předmět: |
Mitochondrial ROS
Umbilical Veins Cell Culture Techniques Peroxisome proliferator-activated receptor Mitochondrion Nitric Oxide medicine.disease_cause Polymerase Chain Reaction Biochemistry Nitric oxide Mice chemistry.chemical_compound Oxygen Consumption Coactivator Genetics medicine Animals Humans Nitric Oxide Donors Molecular Biology Aorta Heat-Shock Proteins chemistry.chemical_classification Reactive oxygen species Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mitochondria Cell biology Mice Inbred C57BL Oxidative Stress NG-Nitroarginine Methyl Ester chemistry Trans-Activators Cattle Endothelium Vascular cGMP-dependent protein kinase Oxidative stress Transcription Factors Biotechnology |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Nitric oxide (NO) has both prooxidant and antioxidant activities in the endothelium; however, the molecular mechanisms involved are still a matter of controversy. PGC-1α [peroxisome proliferators-activated receptor (PPAR) γ coactivator 1-α] 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-1α expression. Short-term (24 h) treatment up-regulates it. Treatment with the NOS inhibitor L-NAME has the opposite effect. Downregulation of PGC-1α 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-1α expression are in all cases paralleled by corresponding variations in the mitochondrial ROS detoxification system. Cells that transiently overexpress PGC-1α from the cytomeglovirus (CMV) promoter respond poorly to NO donors. Analysis of tissues from eNOS-/- mice showed reduced levels of PGC-1α and the mitochondrial ROS detoxification system. These data suggest that NO can regulate the mitochondrial ROS detoxification system both positively and negatively through PGC-1α. This work was supported by an institutional grant from the CNIC, Plan Nacional de I+D+I grants SAF2003–01039, SAF2003–04901, BFI2003–03493, and grant-in-aid from the Spanish Society of Nephrology to S.L. S.B. is a holder of a predoctoral fellowship under grant SAF2003–04901. Inmaculada Valle is a holder of a CNIC-Bancaja predoctoral fellowship. M.M. and S.C. are holders of a Ramon&Cajal contract from the Ministerio de Educación y Ciencia. |
| Databáze: | OpenAIRE |
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