The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s Disease
The cyclic nitroxide TEMPOL exerts anti-oxidative and anti-inflammatory effects, and thus may provide therapeutic benefit in Parkinson’s disease (PD), in which mitochondrial dysfunction, oxidative damage and inflammation have been implicated as pathophysiological mechanisms underlying the selective...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/2/257 |
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| author | Alexander Leathem Martin Simone Joanne M. Dennis Paul K. Witting |
| author_facet | Alexander Leathem Martin Simone Joanne M. Dennis Paul K. Witting |
| author_sort | Alexander Leathem |
| collection | DOAJ |
| description | The cyclic nitroxide TEMPOL exerts anti-oxidative and anti-inflammatory effects, and thus may provide therapeutic benefit in Parkinson’s disease (PD), in which mitochondrial dysfunction, oxidative damage and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons. Markers of oxidative stress and inflammation were investigated in a cell model of differentiated human neuroblastoma (SH-SY5Y) cells treated with the neurotoxin, 6-hydroxydopamine (6-OHDA). Treatment with TEMPOL ameliorated 6-OHDA-mediated cytotoxicity and attenuated biomarkers of oxidative stress including: mitochondrial superoxide anion free radical production, lipid peroxidation, induction of heme oxygenase 1 (HO-1) protein expression and NFκB activation. Treatment with TEMPOL abated decreased gene expression of DRD2S and DRD2L induced by 6-OHDA indicating that TEMPOL may prevent mitochondrial dysfunction and activation of pathways that result in receptor desensitization. 6-OHDA insult decreased gene expression of the antioxidant, SOD-1, and this diminution was also mitigated by TEMPOL. Activation of NFκB increased pro-inflammatory IFNy and decreased IL-6, however, TEMPOL had no effect on these inflammation mediators. Overall, this data suggests that cyclic nitroxides may preserve dopaminergic neuronal cell viability by attenuating oxidative stress and mitochondrial dysfunction, but are unable to affect inflammatory mediators that propagate cellular damage and neurodegeneration in PD. |
| first_indexed | 2024-03-09T22:45:35Z |
| format | Article |
| id | doaj.art-86ac6f2d21d449d281499585bbba9e44 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T22:45:35Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-86ac6f2d21d449d281499585bbba9e442023-11-23T18:30:52ZengMDPI AGAntioxidants2076-39212022-01-0111225710.3390/antiox11020257The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s DiseaseAlexander Leathem0Martin Simone1Joanne M. Dennis2Paul K. Witting3Charles Perkins Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, AustraliaCharles Perkins Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, AustraliaCharles Perkins Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, AustraliaCharles Perkins Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, AustraliaThe cyclic nitroxide TEMPOL exerts anti-oxidative and anti-inflammatory effects, and thus may provide therapeutic benefit in Parkinson’s disease (PD), in which mitochondrial dysfunction, oxidative damage and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons. Markers of oxidative stress and inflammation were investigated in a cell model of differentiated human neuroblastoma (SH-SY5Y) cells treated with the neurotoxin, 6-hydroxydopamine (6-OHDA). Treatment with TEMPOL ameliorated 6-OHDA-mediated cytotoxicity and attenuated biomarkers of oxidative stress including: mitochondrial superoxide anion free radical production, lipid peroxidation, induction of heme oxygenase 1 (HO-1) protein expression and NFκB activation. Treatment with TEMPOL abated decreased gene expression of DRD2S and DRD2L induced by 6-OHDA indicating that TEMPOL may prevent mitochondrial dysfunction and activation of pathways that result in receptor desensitization. 6-OHDA insult decreased gene expression of the antioxidant, SOD-1, and this diminution was also mitigated by TEMPOL. Activation of NFκB increased pro-inflammatory IFNy and decreased IL-6, however, TEMPOL had no effect on these inflammation mediators. Overall, this data suggests that cyclic nitroxides may preserve dopaminergic neuronal cell viability by attenuating oxidative stress and mitochondrial dysfunction, but are unable to affect inflammatory mediators that propagate cellular damage and neurodegeneration in PD.https://www.mdpi.com/2076-3921/11/2/257Parkinson’s diseaseneurodegenerationoxidative stresscyclic nitroxidemitochondrial dysfunctionreactive oxygen species |
| spellingShingle | Alexander Leathem Martin Simone Joanne M. Dennis Paul K. Witting The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s Disease Antioxidants Parkinson’s disease neurodegeneration oxidative stress cyclic nitroxide mitochondrial dysfunction reactive oxygen species |
| title | The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s Disease |
| title_full | The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s Disease |
| title_fullStr | The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s Disease |
| title_full_unstemmed | The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s Disease |
| title_short | The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson’s Disease |
| title_sort | cyclic nitroxide tempol ameliorates oxidative stress but not inflammation in a cell model of parkinson s disease |
| topic | Parkinson’s disease neurodegeneration oxidative stress cyclic nitroxide mitochondrial dysfunction reactive oxygen species |
| url | https://www.mdpi.com/2076-3921/11/2/257 |
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