Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators

St-Pierre, Julie; Drori, Stavit; Uldry, Marc; Silvaggi, Jessica M.; Rhee, James; Jäger, Sibylle; Handschin, Christoph; Zheng, Kangni; Lin, Jiandie D.; Yang, Wenli; Simon, David K.; Bachoo, Robert; Spiegelman, Bruce M.

doi:10.1016/j.cell.2006.09.024

Cited by 1,993 publications

(1,833 citation statements)

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“…38 Previous studies have shown that PGC-1R regulates fundamental metabolic pathways, including fatty acid oxidation, 39 mitochondrial oxidative phosphorylation, 40 gluconeogenesis, 41 and ROS metabolism. 42 For example, PGC-1R is activated to promote expression of genes involved in gluconeogenesis and fatty acid oxidation in hepatocytes upon fasting. 41,43 Similarly, forced expression of PGC-1R in muscle robustly enhances mitochondrial biogenesis, coupled to a shunt of energy dependence on fatty acids.…”

Section: Resultsmentioning

confidence: 99%

Nanosilver Incurs an Adaptive Shunt of Energy Metabolism Mode to Glycolysis in Tumor and Nontumor Cells

Chen

Wang

et al. 2014

ACS Nano

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anomaterials are currently used in a wide range of products with more prospective applications; however, people raised concerns about their safety profiles. This is because nanomaterials have novel physicochemical properties that can interact with biological systems to generate toxicity. 1 To date, most studies have focused on cytotoxicity of nanomaterials at high concentrations that incur significant injuries to cells in vitro and in animals; however, the high dosage used is often not realistic and fails to consider the potentially detrimental effects on human health under chronic lowdose exposure settings, such as everyday and environmental exposure. 2 Thus, research is urgently needed to study the biological effects at sublethal or even nontoxic concentrations. Nanosilver (nAg), a material that is well-known for its antimicrobial properties, has been extensively used in a wide range of biomedical and consumer products. 3À6 Although many studies have been performed to investigate the cytotoxicity of nAg under different settings, 7À9 relatively little study has been conducted to understand the biological effects of nAg under nontoxic concentrations, which likely precede the toxicological processes or can be differentiated from cytotoxic effects but could perturb cellular homeostasis.Under normal conditions, cells maintain a balanced energy homeostasis through concertedly regulated signaling and metabolic pathways. Namely, there is a perfect equilibrium between anabolism and catabolism

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Section: Resultsmentioning

confidence: 99%

Nanosilver Incurs an Adaptive Shunt of Energy Metabolism Mode to Glycolysis in Tumor and Nontumor Cells

Chen

Wang

et al. 2014

ACS Nano

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“…Since the increase of mitochondrial number/activity induced by PGC-1␣ may cause in principle an increase of ROS production, then the protein plays a role in the regulation of the ROS metabolic program, leading to over-expression of ROS detoxifying enzymes, in particular MnSOD (St-Pierre et al, 2006). ROS level in the matrix, where superoxide is mostly released, is thus maintained definitely low to have cells functioning normally.…”

Section: Resultsmentioning

confidence: 99%

An active mitochondrial biogenesis occurs during dendritic cell differentiation

Zaccagnino

Saltarella

Maiorano

et al. 2012

The International Journal of Biochemistry & Cell Biology

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. b s t r a c tDendritic cells (DC) are sentinels of the immune system deriving from circulating monocyte precursors recruited to sites of inflammation. In a previous report (Del Prete et al., 2008) we showed that, after differentiation, DC exhibited increased number of condensed mitochondria and dynamic changes in their energy metabolism. A study is presented here showing that the DC differentiation process is characterized by increased expression level and activity of mitochondrial respiratory complexes, as well as by an increased mitochondrial DNA (mtDNA) copy number. Moreover, DC are equipped with more efficient antioxidant protection systems, over expressed most likely to detoxify increased ROS production, as a consequence of the much higher mitochondrial activity. Kinetic analysis of the three main mitochondrial biogenesis-associated genes revealed that the peak in PPAR␥ coactivator-1alpha (PGC-1␣) gene expression was suddenly reached few hours after the onset of the differentiation. While PGC-1␣ expression rapidly declines, the mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) expression gradually increased. These findings demonstrate that an active mitochondrial biogenesis occurs during DC differentiation and further suggest that an early input by the master regulator of mitochondrial biogenesis PGC-1␣ is needed to trigger the subsequent activation of the downstream transcription factors, NRF-1 and TFAM in this process.

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“…173,175 This might be the reason for the strong expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha in PV þ interneurons, at least during certain stages of brain development. 176,177 Peroxisome proliferatoractivated receptor gamma coactivator 1-alpha has the capability to induce the expression of enzymes involved in glutathione biosynthesis as well as of ROS-detoxifying enzymes such as As a perspective, the functional consequences of metabolic stress in fast-spiking interneurons are illustrated. Even moderate metabolic stress, which occurs either acutely (e.g., hypoxia/ischemia and mitochondrial poisoning) or chronically (e.g., arteriosclerosis or mitochondrial disorders), might cause dramatic decreases in ATP levels and GABA release in fast-spiking interneurons (switch from intermittent to solid blue spheres).…”

Section: Perspective: Metabolic and Oxidative Stress In Fast-spiking mentioning

confidence: 99%

Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

Kann

Papageorgiou

Draguhn

2014

J Cereb Blood Flow Metab

234

235

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Gamma oscillations (B30 to 100 Hz) provide a fundamental mechanism of information processing during sensory perception, motor behavior, and memory formation by coordination of neuronal activity in networks of the hippocampus and neocortex. We review the cellular mechanisms of gamma oscillations about the underlying neuroenergetics, i.e., high oxygen consumption rate and exquisite sensitivity to metabolic stress during hypoxia or poisoning of mitochondrial oxidative phosphorylation. Gamma oscillations emerge from the precise synaptic interactions of excitatory pyramidal cells and inhibitory GABAergic interneurons. In particular, specialized interneurons such as parvalbumin-positive basket cells generate action potentials at high frequency ('fast-spiking') and synchronize the activity of numerous pyramidal cells by rhythmic inhibition ('clockwork'). As prerequisites, fast-spiking interneurons have unique electrophysiological properties and particularly high energy utilization, which is reflected in the ultrastructure by enrichment with mitochondria and cytochrome c oxidase, most likely needed for extensive membrane ion transport and g-aminobutyric acid metabolism. This supports the hypothesis that highly energized fast-spiking interneurons are a central element for cortical information processing and may be critical for cognitive decline when energy supply becomes limited ('interneuron energy hypothesis'). As a clinical perspective, we discuss the functional consequences of metabolic and oxidative stress in fast-spiking interneurons in aging, ischemia, Alzheimer's disease, and schizophrenia.

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Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators

Cited by 1,993 publications

References 42 publications

Nanosilver Incurs an Adaptive Shunt of Energy Metabolism Mode to Glycolysis in Tumor and Nontumor Cells

Nanosilver Incurs an Adaptive Shunt of Energy Metabolism Mode to Glycolysis in Tumor and Nontumor Cells

An active mitochondrial biogenesis occurs during dendritic cell differentiation

Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

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