The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function
<p>Abstract</p> <p>Background</p> <p>Inflammation is known to play a pivotal role in mediating neuronal damage and axonal injury in a variety of neurodegenerative disorders. Among the range of inflammatory mediators, nitric oxide and hydrogen peroxide are potent neuroto...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/9/1/63 |
| _version_ | 1811264732798124032 |
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| author | Gray Elizabeth Ginty Mark Kemp Kevin Scolding Neil Wilkins Alastair |
| author_facet | Gray Elizabeth Ginty Mark Kemp Kevin Scolding Neil Wilkins Alastair |
| author_sort | Gray Elizabeth |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inflammation is known to play a pivotal role in mediating neuronal damage and axonal injury in a variety of neurodegenerative disorders. Among the range of inflammatory mediators, nitric oxide and hydrogen peroxide are potent neurotoxic agents. Recent evidence has suggested that oligodendrocyte peroxisomes may play an important role in protecting neurons from inflammatory damage.</p> <p>Methods</p> <p>To assess the influence of peroxisomal activation on nitric oxide mediated neurotoxicity, we investigated the effects of the peroxisomal proliferator activated receptor (PPAR) gamma agonist, pioglitazone in primary cortical neurons that were either exposed to a nitric oxide donor or co-cultured with activated microglia.</p> <p>Results</p> <p>Pioglitazone protected neurons and axons against both nitric-oxide donor-induced and microglia-derived nitric oxide-induced toxicity. Moreover, cortical neurons treated with this compound showed a significant increase in the protein and gene expression of PPAR-gamma, which was associated with a concomitant increase in the enzymatic activity of catalase. In addition, the protection of neurons and axons against hydrogen peroxide-induced toxicity afforded by pioglitazone appeared to be dependent on catalase.</p> <p>Conclusions</p> <p>Collectively, these observations provide evidence that modulation of PPAR-gamma activity and peroxisomal function by pioglitazone attenuates both NO and hydrogen peroxide-mediated neuronal and axonal damage suggesting a new therapeutic approach to protect against neurodegenerative changes associated with neuroinflammation.</p> |
| first_indexed | 2024-04-12T20:09:39Z |
| format | Article |
| id | doaj.art-e9907a6bbd7f4a4890721e4252e5a590 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-12T20:09:39Z |
| publishDate | 2012-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-e9907a6bbd7f4a4890721e4252e5a5902022-12-22T03:18:17ZengBMCJournal of Neuroinflammation1742-20942012-04-01916310.1186/1742-2094-9-63The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal functionGray ElizabethGinty MarkKemp KevinScolding NeilWilkins Alastair<p>Abstract</p> <p>Background</p> <p>Inflammation is known to play a pivotal role in mediating neuronal damage and axonal injury in a variety of neurodegenerative disorders. Among the range of inflammatory mediators, nitric oxide and hydrogen peroxide are potent neurotoxic agents. Recent evidence has suggested that oligodendrocyte peroxisomes may play an important role in protecting neurons from inflammatory damage.</p> <p>Methods</p> <p>To assess the influence of peroxisomal activation on nitric oxide mediated neurotoxicity, we investigated the effects of the peroxisomal proliferator activated receptor (PPAR) gamma agonist, pioglitazone in primary cortical neurons that were either exposed to a nitric oxide donor or co-cultured with activated microglia.</p> <p>Results</p> <p>Pioglitazone protected neurons and axons against both nitric-oxide donor-induced and microglia-derived nitric oxide-induced toxicity. Moreover, cortical neurons treated with this compound showed a significant increase in the protein and gene expression of PPAR-gamma, which was associated with a concomitant increase in the enzymatic activity of catalase. In addition, the protection of neurons and axons against hydrogen peroxide-induced toxicity afforded by pioglitazone appeared to be dependent on catalase.</p> <p>Conclusions</p> <p>Collectively, these observations provide evidence that modulation of PPAR-gamma activity and peroxisomal function by pioglitazone attenuates both NO and hydrogen peroxide-mediated neuronal and axonal damage suggesting a new therapeutic approach to protect against neurodegenerative changes associated with neuroinflammation.</p>http://www.jneuroinflammation.com/content/9/1/63PeroxisomeNitric oxidePioglitazonePeroxisome proliferator activated receptor |
| spellingShingle | Gray Elizabeth Ginty Mark Kemp Kevin Scolding Neil Wilkins Alastair The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function Journal of Neuroinflammation Peroxisome Nitric oxide Pioglitazone Peroxisome proliferator activated receptor |
| title | The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function |
| title_full | The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function |
| title_fullStr | The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function |
| title_full_unstemmed | The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function |
| title_short | The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function |
| title_sort | ppar gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function |
| topic | Peroxisome Nitric oxide Pioglitazone Peroxisome proliferator activated receptor |
| url | http://www.jneuroinflammation.com/content/9/1/63 |
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