Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation
Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, disp...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/3/357 |
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| author | Mojca Trstenjak Prebanda Petra Matjan-Štefin Boris Turk Nataša Kopitar-Jerala |
| author_facet | Mojca Trstenjak Prebanda Petra Matjan-Štefin Boris Turk Nataša Kopitar-Jerala |
| author_sort | Mojca Trstenjak Prebanda |
| collection | DOAJ |
| description | Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease. |
| first_indexed | 2024-03-09T06:19:28Z |
| format | Article |
| id | doaj.art-19fca2cb0d3948eeac58c555f8cd694c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T06:19:28Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-19fca2cb0d3948eeac58c555f8cd694c2023-12-03T11:49:18ZengMDPI AGAntioxidants2076-39212021-02-0110335710.3390/antiox10030357Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced NeuroinflammationMojca Trstenjak Prebanda0Petra Matjan-Štefin1Boris Turk2Nataša Kopitar-Jerala3Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, SI-1000 Ljubljana, SloveniaDepartment of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, SI-1000 Ljubljana, SloveniaDepartment of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, SI-1000 Ljubljana, SloveniaDepartment of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, SI-1000 Ljubljana, SloveniaStefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease.https://www.mdpi.com/2076-3921/10/3/357braincystatinEPM1neuro inflammationLPS-induced oxidative stressperoxiredoxin |
| spellingShingle | Mojca Trstenjak Prebanda Petra Matjan-Štefin Boris Turk Nataša Kopitar-Jerala Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation Antioxidants brain cystatin EPM1 neuro inflammation LPS-induced oxidative stress peroxiredoxin |
| title | Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation |
| title_full | Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation |
| title_fullStr | Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation |
| title_full_unstemmed | Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation |
| title_short | Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation |
| title_sort | altered expression of peroxiredoxins in mouse model of progressive myoclonus epilepsy upon lps induced neuroinflammation |
| topic | brain cystatin EPM1 neuro inflammation LPS-induced oxidative stress peroxiredoxin |
| url | https://www.mdpi.com/2076-3921/10/3/357 |
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