Abstract：
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a lysosomal storage disease caused by mutations in the gene encoding the enzyme iduronate 2-sulfatase (IDS) and biochemically characterized by the accumulation of glycosaminoglycans (GAGs) in different tissues. It is a multisystemic disorder that presents liver abnormalities, the pathophysiology of which is not yet established. In the present study, we evaluated bioenergetics, redox homeostasis, and mitochondrial dynamics in the liver of 6-month-old MPS II mice (IDS-). Our findings show a decrease in the activity of α-ketoglutarate dehydrogenase and an increase in the activities of succinate dehydrogenase and malate dehydrogenase. The activity of mitochondrial complex I was also increased whereas the other complex activities were not affected. In contrast, mitochondrial respiration, membrane potential, ATP production, and calcium retention capacity were not altered. Furthermore, malondialdehyde levels and 2\',7\'-dichlorofluorescein oxidation were increased in the liver of MPS II mice, indicating lipid peroxidation and increased ROS levels, respectively. Sulfhydryl and reduced glutathione levels, as well as glutathione S-transferase, glutathione peroxidase (GPx), superoxide dismutase, and catalase activities were also increased. Finally, the levels of proteins involved in mitochondrial mass and dynamics were decreased in knockout mice liver. Taken together, these data suggest that alterations in energy metabolism, redox homeostasis, and mitochondrial dynamics can be involved in the pathophysiology of liver abnormalities observed in MPS II.
摘要：
II型粘多糖贮积症（MPSII；Hunter综合征）是一种溶酶体贮积病，由编码艾杜糖醛酸2-硫酸酯酶（IDS）的基因突变引起，其生化特征是糖胺聚糖（GAG）在不同组织中的积累。这是一种表现为肝脏异常的多系统疾病，其病理生理学尚未建立。在本研究中,我们评估了生物能学，氧化还原稳态，6个月大的MPSII小鼠（IDS-）肝脏中的线粒体动力学。我们的发现表明α-酮戊二酸脱氢酶的活性降低，琥珀酸脱氢酶和苹果酸脱氢酶的活性增加。线粒体复合物I的活性也增加，而其他复合物活性则不受影响。相比之下,线粒体呼吸，膜电位，ATP生产，钙保留能力没有改变。此外，丙二醛水平和2'，7'-二氯荧光素氧化在MPSII小鼠的肝脏中增加，表明脂质过氧化和增加的ROS水平，分别。巯基和还原型谷胱甘肽水平，以及谷胱甘肽S-转移酶，谷胱甘肽过氧化物酶（GPx），超氧化物歧化酶,过氧化氢酶活性也增加。最后,基因敲除小鼠肝脏中与线粒体质量和动力学有关的蛋白质水平降低。一起来看,这些数据表明能量代谢的改变，氧化还原稳态，和线粒体动力学可以参与在MPSII中观察到的肝脏异常的病理生理学。
