Trstenjak Prebanda Mojca, Matjan-Štefin Petra, Turk Boris, Kopitar-Jerala Nataša
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, SI-1000 Ljubljana, Slovenia.
International Postgraduate School Jožef Stefan, Jamova 39, SI-1000 Ljubljana, Slovenia.
Antioxidants (Basel). 2021 Feb 27;10(3):357. doi: 10.3390/antiox10030357.
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.
斯德芬B（胱抑素B）是一种内溶酶体半胱氨酸组织蛋白酶抑制剂，在患有进行性肌阵挛癫痫的一种类型——昂韦里希特-伦德伯格病（EPM1）的患者中，已报道了斯德芬B基因的功能丧失突变。斯德芬B基因缺陷小鼠是该疾病的一种小鼠模型，表现出EPM1的关键特征，包括肌阵挛发作。尽管其潜在机制尚未完全明确，但据报道，大脑中氧化还原稳态受损和炎症会导致疾病进展。在本研究中，我们调查了脂多糖（LPS）引发的神经炎症是否会影响斯德芬B基因缺陷小鼠大脑和小脑内氧化还原敏感蛋白的水平，这些蛋白包括硫氧还蛋白（Trx1）、硫氧还蛋白还原酶（TrxR）、过氧化物酶（Prxs）。结果发现，LPS刺激导致斯德芬B基因缺陷小鼠大脑和小脑内的Trx1和TrxR显著升高，而LPS刺激后仅小脑内的Prx1上调。未受刺激的斯德芬B基因缺陷小鼠制备的小脑组织裂解物中线粒体过氧化物酶3（Prx3）也上调，而LPS刺激后，斯德芬B基因缺陷小鼠的大脑和小脑内Prx3上调。我们的结果表明氧化应激在该疾病进展中发挥作用。
