PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cells
I Valle, A Alvarez-Barrientos, E Arza… - Cardiovascular …, 2005 - academic.oup.com
I Valle, A Alvarez-Barrientos, E Arza, S Lamas, M Monsalve
Cardiovascular research, 2005•academic.oup.comObjective: Mitochondrial production of oxidants contributes to a variety of pathological
conditions including the vascular complications of diabetes, neurodegenerative diseases,
and cellular senescence. We postulated that a transcriptional coactivator, peroxisome
proliferator activated receptor-γ coactivator 1α (PGC-1α), a major regulator of oxidative
metabolism and mitochondrial biogenesis, could be involved in the transcriptional regulation
of the mitochondrial antioxidant defense system in vascular endothelial cells. Methods and …
conditions including the vascular complications of diabetes, neurodegenerative diseases,
and cellular senescence. We postulated that a transcriptional coactivator, peroxisome
proliferator activated receptor-γ coactivator 1α (PGC-1α), a major regulator of oxidative
metabolism and mitochondrial biogenesis, could be involved in the transcriptional regulation
of the mitochondrial antioxidant defense system in vascular endothelial cells. Methods and …
Abstract
Objective: Mitochondrial production of oxidants contributes to a variety of pathological conditions including the vascular complications of diabetes, neurodegenerative diseases, and cellular senescence. We postulated that a transcriptional coactivator, peroxisome proliferator activated receptor-γ coactivator 1α (PGC-1α), a major regulator of oxidative metabolism and mitochondrial biogenesis, could be involved in the transcriptional regulation of the mitochondrial antioxidant defense system in vascular endothelial cells.
Methods and results: We show that PGC-1α is present in human, bovine, and mouse endothelial cells and positively modulates the expression of the mitochondrial detoxification system. Endothelial cells that overexpress PGC-1α show reduced accumulation of reactive oxygen species (ROS), increased mitochondrial membrane potential, and reduced apoptotic cell death both in basal and oxidative stress conditions. Downregulation of PGC-1α levels by siRNA reduces the expression of mitochondrial detoxification proteins.
Conclusions: These results unveil a novel regulatory pathway that links mitochondrial activity and mitochondrial oxidative stress protective systems. In addition, they suggest that PGC-1α could play a crucial protective role in vascular complications of diabetes, where the mitochondrial metabolism of glucose has been shown to result in oxidative stress and vascular endothelial cell dysfunction.
Oxford University Press