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Front. Pharmacol. | doi: 10.3389/fphar.2019.00947

Protective effects of lanosterol synthase up-regulation in UV-B induced oxidative stress.

Hui Hua1, Tianyao Yang1, Liting Huang1, Rentong Chen1, Menglin Li1, Zhenzhen Zou1, Nan Wang1, Dan Yang1 and  Yang Liu1*
  • 1China Medical University, China

UV-B radiation may be an important risk factor in cataracts aetiology. 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 expression 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 cataracts prevention.

Keywords: UV-B, Lanosterol synthase, Crystallin, Oxidative Stress, Apoptosis

Received: 18 Feb 2019; Accepted: 24 Jul 2019.

Edited by:

Andres Trostchansky, Faculty of Medicine, University of the Republic, Uruguay

Reviewed by:

Manlio Vinciguerra, International Clinical Research Center (FNUSA-ICRC), Czechia
Sanguine Byun, Incheon National University, South Korea  

Copyright: © 2019 Hua, Yang, Huang, Chen, Li, Zou, Wang, Yang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yang Liu, China Medical University, Shenyang, 110001, Liaoning Province, China, yangliu@cmu.edu.cn