Protective Effects of Lanosterol Synthase Up-Regulation in UV-B-Induced Oxidative Stress

Abstract

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.

The Intravitreal Injection of Lanosterol Nanoparticles Rescues Lens Structure Collapse at an Early Stage in Shumiya Cataract Rats

“…Recently, it was reported that the administration of lanosterol plays a protective role in the early stages of crystallin denaturation and lens epithelial cell apoptosis by oxidative-damage-induced UV-B exposure [7]. Huang et al showed that a combination of lanosterol and hesperetin is effective in delaying selenite-induced cataracts [8].…”

“…On the other hand, Kang et al reported that lanosterol disrupts the aggregation of human γD-crystallin by binding to the hydrophobic dimerization interface and is likely correlated with oxidative stress processes [6]. In addition, lanosterol can play a protective role during the early stages of crystallin denaturation and lens epithelial cell apoptosis through oxidative-damage-induced UV-B exposure [7]. Huang et al also reported that a combination of lanosterol and hesperetin is effective in delaying selenite-induced cataracts [8].…”

Cytoprotective role of humanin in lens epithelial cell oxidative stress‑induced injury

“…The present study revealed that Hn was expressed in Hlecs and responded to oxidative stress. The level of roS in Hlecs has previously been reported to be positively associated with the dose of uVB and induced different degrees of oxidative stress in cells (27). The results indicated that 4-12 h after uVB irradiation, Hn expression increased, which was associated with uVB irradiation.…”

<p>Agonism of Gpr40 Protects the Capacities of Epidermal Stem Cells (ESCs) Against Ultraviolet-B (UV-B)</p>

“…Recent studies utilizing murine models have demonstrated the role of ROS in UV-B-induced insult in a variety of diseases ranging from skin cancer to cataracts. 22,23 Indeed, UV-B overexposure even induces oxidative stress in flora, demonstrating the over-arching risk of ROS overproduction due to UV-B. 24 This prevalent oxidative stressinducing ability of UV-B is, therefore, a key point of focus in the search for therapies to mitigate UV-Binduced injury.…”