Protective Effects of Lanosterol Synthase Up-Regulation in UV-B-Induced Oxidative Stress
Protective Effects of Lanosterol Synthase Up-Regulation in UV-B-Induced Oxidative Stress
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羊毛甾醇合酶上调对 UV-B 诱导的氧化应激的保护作用
DOI：
10.3389/fphar.2019.00947
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发表时间：
2019-08-29
影响因子：
5.6
通讯作者：
Liu, Yang
中科院分区：
文献类型：
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作者：
Hua, Hui;Yang, Tianyao;Liu, Yang
UV-B辐射可能是白内障发病的重要危险因素。在暴露于UV-B辐射后，细胞在修复DNA损伤方面表现出不平衡，这引起某些蛋白质水平的变化，包括α-晶状体蛋白，它是透镜中最丰富的蛋白质，对维持透镜的透明度至关重要。羊毛甾醇合成酶（LSS）是胆固醇生物合成中一种重要的限速酶，可能在氧化应激和维持透镜透明度方面发挥重要作用。然而，LSS在UV-B诱导的细胞凋亡中的作用尚不清楚。因此，我们用紫外线照射雌性Sprague-Dawley大鼠，以建立一个动物模型，探讨LSS表达的变化在UV-B暴露的早期阶段。此外，我们培养过表达LSS的人透镜上皮细胞（HLE），并将其暴露于UV-B辐射，以探讨LSS表达增加在UV-B诱导的细胞凋亡中的作用。这些数据表明，UV-B暴露诱导氧化应激和凋亡大鼠透镜上皮细胞和辐射暴露增加晶状体损伤的水平。UV-B暴露降低了α-晶状体蛋白的含量，增加了Bax和caspase-3的表达。UV-B照射后，过表达LSS的HLE细胞的凋亡相关指数低于对照细胞。此外，活性氧的过量产生可能会激活sirtuin 1（Sirt 1）途径，从而诱导蛋白质表达的固醇调节元件结合转录因子2（SREBF 2），3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR），和LSS。然而，Sirt 1通路的具体机制需要进一步研究。可见，UV-B暴露可诱导透镜上皮细胞氧化损伤，导致晶状体蛋白变性和凋亡，LSS可能在此过程的早期阶段起保护作用，可作为白内障防治的重要靶点。
UV-B radiation may be an important risk factor in cataract etiology. After exposure to UV-B radiation, cells show imbalances in the repair of DNA damage, which induce changes in the levels of certain proteins, including alpha-crystallin, which is the most abundant protein in the lens and crucial for the maintenance of lens transparency. Lanosterol synthase (LSS), an essential rate-limiting enzyme in cholesterol biosynthesis, might play significant roles in oxidative stress and in the maintenance of lens transparency. However, the roles of LSS in UV-B-induced apoptosis are not well understood. Therefore, we irradiated female Sprague-Dawley rats with ultraviolet radiation to establish an animal model for exploring the variations in LSS expression during the early stages of UV-B exposure. In addition, we cultured human lens epithelial (HLE) cells that overexpress LSS and exposed them to UV-B radiation to explore the function of increased LSS expression in UV-B-induced apoptosis. The data demonstrated that UV-B exposure induced oxidative stress and apoptosis in rat lens epithelial cells and that irradiance exposure increased the level of lenticular damage. Additionally, UV-B exposure decreased the alpha-crystallin content and increased the expressions of Bax and cleaved caspase-3 compared with the control levels. After exposure to UV-B, the apoptosis-related index of HLE cells overexpressing LSS was lower than that of the control cells. Furthermore, ROS overproduction might activate the sirtuin 1 (Sirt1) pathway, which induced protein expressions of sterol regulatory element-binding transcription factor 2 (SREBF2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and LSS. However, the specific mechanism of the Sirt1 pathway needed to be further studied. In summary, UV-B exposure induced oxidative injury and resulted in crystallin denaturation and apoptosis in lens epithelial cells, and LSS might play a protective role during the early stages of this process and could be an important target in the cataract prevention.