Aleksic Marija, Kalezic Andjelika, Saso Luciano, Jankovic Aleksandra, Korac Bato, Korac Aleksandra
Center for Electron Microscopy, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.
Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
Antioxidants (Basel). 2021 Apr 12;10(4):591. doi: 10.3390/antiox10040591.
Brown adipose tissue (BAT) is important for maintaining whole-body metabolic and energy homeostasis. However, the effects of hypothyroidism, one of the most common diseases worldwide, which increases the risk of several metabolic disorders, on BAT redox and metabolic homeostasis remain mostly unknown. We aimed to investigate the dynamics of protein expression, enzyme activity, and localization of antioxidant defense (AD) enzymes in rat interscapular BAT upon induction of hypothyroidism by antithyroid drug methimazole for 7, 15, and 21 days. Our results showed an increased protein expression of CuZn- and Mn-superoxide dismutase, catalase, glutamyl-cysteine ligase, thioredoxin, total glutathione content, and activity of catalase and thioredoxin reductase in hypothyroid rats, compared to euthyroid control. Concomitant with the increase in AD, newly established nuclear, mitochondrial, and peroxisomal localization of AD enzymes was found. Hypothyroidism also potentiated associations between mitochondria, peroxisomes, and lipid bodies, creating specific structural-functional units. Moreover, hypothyroidism induced protein expression and nuclear translocation of a master regulator of redox-metabolic homeostasis, nuclear factor erythroid 2-related factor 2 (Nrf2), and an increased amount of 4-hydroxynonenal (4-HNE) protein adducts. The results indicate that spatiotemporal overlap in the remodeling of AD is orchestrated by Nrf2, implicating the role of 4-HNE in this process and suggesting the potential mechanism of redox-structural remodeling during BAT adaptation in hypothyroidism.
棕色脂肪组织（BAT）对于维持全身代谢和能量稳态至关重要。然而，甲状腺功能减退症作为全球最常见的疾病之一，会增加多种代谢紊乱的风险，其对BAT氧化还原和代谢稳态的影响仍大多未知。我们旨在研究用抗甲状腺药物甲巯咪唑诱导大鼠甲状腺功能减退7天、15天和21天后，肩胛间BAT中蛋白质表达、酶活性及抗氧化防御（AD）酶定位的动态变化。我们的结果显示，与甲状腺功能正常的对照组相比，甲状腺功能减退大鼠中铜锌超氧化物歧化酶、锰超氧化物歧化酶、过氧化氢酶、谷氨酰半胱氨酸连接酶、硫氧还蛋白、总谷胱甘肽含量以及过氧化氢酶和硫氧还蛋白还原酶的活性均有所增加。伴随AD的增加，还发现了AD酶新建立的核、线粒体和过氧化物酶体定位。甲状腺功能减退还增强了线粒体、过氧化物酶体和脂质体之间的联系，形成了特定的结构 - 功能单位。此外，甲状腺功能减退诱导了氧化还原 - 代谢稳态的主要调节因子核因子红细胞2相关因子2（Nrf2）的蛋白质表达和核转位，以及4 - 羟基壬烯醛（4 - HNE）蛋白质加合物数量的增加。结果表明，AD重塑的时空重叠由Nrf2协调，这暗示了4 - HNE在此过程中的作用，并提示了甲状腺功能减退时BAT适应过程中氧化还原 - 结构重塑的潜在机制。
