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Peroxisome proliferator-activated receptor (PPAR) γ and PPARα agonists modulate mitochondrial fusion-fission dynamics: relevance to reactive oxygen species (ROS)-related neurodegenerative disorders?

Zolezzi, Juan M ; Silva-Alvarez, Carmen ; Ordenes, Daniela ; Godoy, Juan A ; Carvajal, Francisco J ; Santos, Manuel J ; Inestrosa, Nibaldo C Ferreira, Sergio T.

PloS one, 2013-05, Vol.8 (5), p.e64019 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Peroxisome proliferator-activated receptor (PPAR) γ and PPARα agonists modulate mitochondrial fusion-fission dynamics: relevance to reactive oxygen species (ROS)-related neurodegenerative disorders?
Autor: Zolezzi, Juan M ; Silva-Alvarez, Carmen ; Ordenes, Daniela ; Godoy, Juan A ; Carvajal, Francisco J ; Santos, Manuel J ; Inestrosa, Nibaldo C
Ferreira, Sergio T.
Assuntos: Alzheimer's disease ; Animal cognition ; Animals ; Apolipoprotein E ; Biology ; Brain ; Brain research ; Cancer ; Cognitive ability ; Disease ; Disorders ; Dynamic tests ; Dynamics ; Dynamin ; Dynamins - genetics ; Dynamins - metabolism ; Embryo, Mammalian ; Experiments ; FDA approval ; Fission ; Gene expression ; Gene Expression Regulation ; Hippocampus ; Hippocampus - cytology ; Hippocampus - drug effects ; Hippocampus - metabolism ; Immunofluorescence ; Medicine ; Metabolism ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - genetics ; Mitochondria - metabolism ; Mitochondria - ultrastructure ; Mitochondrial DNA ; Mitochondrial Dynamics - drug effects ; Mitochondrial Dynamics - genetics ; Mitochondrial Proteins - genetics ; Mitochondrial Proteins - metabolism ; Neurodegeneration ; Neurodegenerative diseases ; Neuromodulation ; Neurons ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Oxidative Stress ; Oxygen ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Peroxisome proliferator-activated receptors ; PPAR alpha - agonists ; PPAR alpha - genetics ; PPAR alpha - metabolism ; PPAR gamma - agonists ; PPAR gamma - genetics ; PPAR gamma - metabolism ; Pretreatment ; Primary Cell Culture ; Proteins ; Pyrimidines - pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Receptors ; Rodents ; Therapy ; Thiazolidinediones - pharmacology ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transgenic mice
É parte de: PloS one, 2013-05, Vol.8 (5), p.e64019
Notas: Competing Interests: The authors have declared that no competing interests exists.
Conceived and designed the experiments: JMZ DO JAG NCI. Performed the experiments: JMZ CSA DO JAG FJC. Analyzed the data: JMZ DO FJC. Contributed reagents/materials/analysis tools: CSA MJS NCI. Wrote the paper: JMZ CSA DO MJS NCI.
Descrição: Recent studies showed that the activation of the retinoid X receptor, which dimerizes with peroxisome proliferator-activated receptors (PPARs), leads to an enhanced clearance of Aβ from the brain of transgenic mice model of Alzheimer's disease (AD), because an increased expression of apolipoprotein E and it main transporters. However, the effects observed must involve additional underlying mechanisms that have not been yet explored. Several studies conducted in our laboratory suggest that part of the effects observed for the PPARs agonist might involves mitochondrial function and, particularly, mitochondrial dynamics. In the present study we assessed the effects of oxidative stress challenge on mitochondrial morphology and mitochondrial dynamics-related proteins in hippocampal neurons. Using immunofluorescence, we evaluated the PPARγ co-activator 1α (PGC-1α), dynamin related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), and mitochondrial length, in order to determine if PPARs agonist pre-treatment is able to protect mitochondrial population from hippocampal neurons through modulation of the mitochondrial fusion-fission events. Our results suggest that both a PPARγ agonist (ciglitazone) and a PPARα agonist (WY 14.643) are able to protect neurons by modulating mitochondrial fusion and fission, leading to a better response of neurons to oxidative stress, suggesting that a PPAR based therapy could acts simultaneously in different cellular components. Additionally, our results suggest that PGC-1α and mitochondrial dynamics should be further studied in future therapy research oriented to ameliorate neurodegenerative disorders, such as AD.
Editor: United States: Public Library of Science
Idioma: Inglês

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Peroxisome proliferator-activated receptor (PPAR) γ and PPARα agonists modulate mitochondrial fusion-fission dynamics: relevance to reactive oxygen species (ROS)-related neurodegenerative disorders?

Zolezzi, Juan M ; Silva-Alvarez, Carmen ; Ordenes, Daniela ; Godoy, Juan A ; Carvajal, Francisco J ; Santos, Manuel J ; Inestrosa, Nibaldo C Ferreira, Sergio T.

United States: Public Library of Science

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