Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages
Stefin B (cystatin B) is an intracellular inhibitor of cysteine cathepsins and mutations in the stefin B gene, resulting in the development of Unverricht−Lundborg disease, which is a form of myoclonic epilepsy. It was suggested that a key mechanism behind stefin B-mediated disease progress...
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doaj-d4efcc04847f47afaafd542d759677222020-11-25T01:24:53ZengMDPI AGCells2073-44092019-11-01812147610.3390/cells8121476cells8121476Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient MacrophagesMojca Trstenjak Prebanda0Janja Završnik1Boris 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 intracellular inhibitor of cysteine cathepsins and mutations in the stefin B gene, resulting in the development of Unverricht−Lundborg disease, which is a form of myoclonic epilepsy. It was suggested that a key mechanism behind stefin B-mediated disease progression was impaired redox homeostasis. Stefin B-deficient mice were found more sensitive to lipopolysaccharide (LPS)-induced sepsis as a consequence of increased expression of caspase-11 and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing (NLRP nflammasome activation and higher levels of mitochondrial reactive oxygen species (ROS). In the present study, we investigated if LPS-triggered oxidative stress affected the protein levels and redox status of redox sensitive proteins—thioredoxin, peroxiredoxins, and superoxide dismutases in macrophages and spleens of LPS-injected mice. LPS challenge was found to result in a marked elevation in mitochondrial peroxiredoxin 3 (Prx3), sulfiredoxin, and superoxide dismutase 2 (Sod2) in stefin B-deficient macrophages and spleens. We determined that sulfiredoxin is targeted to mitochondria after LPS challenge. In conclusion, the upregulation of mitochondrial redox-sensitive proteins Prx3 and Sod2 in stefin B-deficient cells implies a protective role of stefin B in mitochondrial function.https://www.mdpi.com/2073-4409/8/12/1476cystatininflammationlps-induced oxidative stress, peroxiredoxinsulfiredoxinsuperoxide dismutasesthioredoxin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mojca Trstenjak Prebanda Janja Završnik Boris Turk Nataša Kopitar Jerala |
spellingShingle |
Mojca Trstenjak Prebanda Janja Završnik Boris Turk Nataša Kopitar Jerala Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages Cells cystatin inflammation lps-induced oxidative stress, peroxiredoxin sulfiredoxin superoxide dismutases thioredoxin |
author_facet |
Mojca Trstenjak Prebanda Janja Završnik Boris Turk Nataša Kopitar Jerala |
author_sort |
Mojca Trstenjak Prebanda |
title |
Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages |
title_short |
Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages |
title_full |
Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages |
title_fullStr |
Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages |
title_full_unstemmed |
Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages |
title_sort |
upregulation of mitochondrial redox sensitive proteins in lps-treated stefin b-deficient macrophages |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2019-11-01 |
description |
Stefin B (cystatin B) is an intracellular inhibitor of cysteine cathepsins and mutations in the stefin B gene, resulting in the development of Unverricht−Lundborg disease, which is a form of myoclonic epilepsy. It was suggested that a key mechanism behind stefin B-mediated disease progression was impaired redox homeostasis. Stefin B-deficient mice were found more sensitive to lipopolysaccharide (LPS)-induced sepsis as a consequence of increased expression of caspase-11 and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing (NLRP nflammasome activation and higher levels of mitochondrial reactive oxygen species (ROS). In the present study, we investigated if LPS-triggered oxidative stress affected the protein levels and redox status of redox sensitive proteins—thioredoxin, peroxiredoxins, and superoxide dismutases in macrophages and spleens of LPS-injected mice. LPS challenge was found to result in a marked elevation in mitochondrial peroxiredoxin 3 (Prx3), sulfiredoxin, and superoxide dismutase 2 (Sod2) in stefin B-deficient macrophages and spleens. We determined that sulfiredoxin is targeted to mitochondria after LPS challenge. In conclusion, the upregulation of mitochondrial redox-sensitive proteins Prx3 and Sod2 in stefin B-deficient cells implies a protective role of stefin B in mitochondrial function. |
topic |
cystatin inflammation lps-induced oxidative stress, peroxiredoxin sulfiredoxin superoxide dismutases thioredoxin |
url |
https://www.mdpi.com/2073-4409/8/12/1476 |
work_keys_str_mv |
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