Peroxisome Proliferator-Activated Receptor γ Agonists Accelerate Oligodendrocyte Maturation and Influence Mitochondrial Functions and Oscillatory Ca2+Waves
| Autor: | Luisa Minghetti, Sergio Visentin, Chiara De Nuccio, Enrico Mancuso, Valerio Magnaghi, Antonietta Bernardo, Roberta De Simone |
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| Rok vydání: | 2011 |
| Předmět: |
Peroxisome proliferator-activated receptor
Mitochondrion Pathology and Forensic Medicine Electron Transport Complex IV Cellular and Molecular Neuroscience Prosencephalon Biological Clocks Organometallic Compounds medicine Animals Mitochondrial respiratory chain complex I Rats Wistar Cells Cultured Membrane Potential Mitochondrial chemistry.chemical_classification Aniline Compounds Pioglitazone biology Prostaglandin D2 Stem Cells Mitochondrial respiratory chain complex IV Cell Differentiation Myelin Basic Protein General Medicine Peroxisome Oligodendrocyte Mitochondria Rats Myelin basic protein Cell biology PPAR gamma Oligodendroglia medicine.anatomical_structure Mitochondrial respiratory chain Animals Newborn Gene Expression Regulation Xanthenes Neurology chemistry Biochemistry biology.protein Calcium Thiazolidinediones Neurology (clinical) |
| Zdroj: | Journal of Neuropathology & Experimental Neurology. 70:900-912 |
| ISSN: | 1554-6578 0022-3069 |
| DOI: | 10.1097/nen.0b013e3182309ab1 |
| Popis: | We have previously shown that natural (15-deoxy-Δ12,14-prostaglandin J2) and synthetic (pioglitazone) agonists of peroxisome proliferator-activated receptor γ (PPAR-γ) strengthen the intrinsic cellular mechanisms protecting oligodendrocyte (OL) progenitors (OPs) from oxidative insults and promote their differentiation. Here, we demonstrate that repeated administrations of PPAR-γ agonists to OP cultures accelerate their differentiation to OLs, as indicated by increased numbers of O4- and O1-positive cells that show increased myelin basic protein expression, elaborated cholesterol-enrichedmembranes and have increased peroxisomes. Moreover, PPAR-γ agonist-treated OLs show increased activity of the mitochondrial respiratory chain Complex IV and an increased ability to respond to environmental signals, such as adenosine diphosphate (ADP), with oscillatory Ca2+ waves; the latter closely correlated with the presence of mitochondria and were inhibited by the mitochondrial respiratory chain Complex I inhibitor rotenone. Because Ca2+ oscillations and mitochondrial respiratory chain activity play crucial roles in OL differentiation, these findings suggest that PPAR-γ agonists could protect OLs and promote myelination through several mechanisms, including those involving mitochondrial functions. Our studies support the therapeutic potential of PPAR-γ agonists in brain diseases in which mitochondrial alteration, oxidative stress, and demyelination occur and point to the need for a better understanding of the role of PPAR-γ and its agonists in OL biology. |
| Databáze: | OpenAIRE |
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