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.
Highlights
Cataracts, which are predominantly related to the aging process (Zelentsova et al, 2017), remain the leading cause of legal blindness worldwide (Organization World Health; Bebbington, 2001)Epidemiological data showed that ultraviolet (UV) radiation was an important risk factor in cataract etiology (Delcourt et al, 2014) and could increase the global disease burdenEffects of Lanosterol synthase (LSS) in Lens (Lucas et al, 2008)
The following immunoblotting antibodies were used: antibodies against Bcl-2-associated X protein (Bax), cleaved caspase-3, and beta-actin were purchased from CST, and antibodies against B cell lymphoma-2 (Bcl-2), sterol regulatory element-binding factor 2 (SREBF2), LSS, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), crystallin A (CRYAA)&crystallin B (CRYAB), and Sirtuin1 (Sirt1) and goat antirabbit IgG H&L (HRP) secondary antibody were obtained from Abcam (Cambridge, UK)
UV radiation B (UV-B) treatment induced proliferation of the lens epithelial cells, and the analysis of the cells exposed to UV-B revealed irregular nuclei and intercellular spaces with many vesicles and water splits
Summary
Cataracts, which are predominantly related to the aging process (Zelentsova et al, 2017), remain the leading cause of legal blindness worldwide (Organization World Health; Bebbington, 2001)Epidemiological data showed that ultraviolet (UV) radiation was an important risk factor in cataract etiology (Delcourt et al, 2014) and could increase the global disease burdenEffects of LSS in Lens (Lucas et al, 2008). Alpha-crystallin B (CRYAB) reportedly prevented H2O2induced apoptosis in cardiac H9c2 cells (Xu et al, 2013), and alpha-crystallin A (CRYAA) blocked UV-A-induced apoptosis by activating the Akt survival pathway (Liu et al, 2004) Mutations in these crystallin proteins could cause cataracts (Mori et al, 2006). Lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase; LSS) catalyzes lanosterol formation, which was a key rate-limiting step in cholesterol biosynthesis (Huff and Telford, 2005; Nes, 2011).The incubation of Ganoderma lucidum with the pro-oxidant 1-chloro-2,4dinitrobenzene could reduce LSS mRNA expression (You et al, 2012) These findings indicated that LSS might play significant roles in oxidative stress and the maintenance of lens transparency. The expression changes, and the roles of LSS in ROS-induced oxidative stress processes are not well known
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