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Jing-Ying Xu, Yiting YANG, Peng Shang, Chaoyang Zhang, qingjian Ou, Furong Gao, Haibin Tian, Caixia Jin, Lixia Lu, Guo-Tong Xu; ATF3 inhibiting ASNS expression Contributes to Naphthalene Induced Cataract Development. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5644. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Naphthalene induced cataract model is widely used to clarify the etiology of age-related cataract. In this work, the roles of ASNS (Asparagine synthase) and its upstream regulation factor ATF3 ( activating transcription factor 3) in the cataract development were investigated in naphthalene induced cataract rat model.
An induced cataract model was established by intragastric administration of naphthalene. A slit lamp biomicroscopy examination was performed on rats every week after naphthalene exposure. Microarray was used to identify differentially expressed mRNA in lens between naphthalene treated rats and control groups. Furthermore, the expression levels of interested genes were verified by real time-PCR and western blot. The metabolites of naphthalene was measured with NADP/NADPH assay kit. The protective function of ASNS on cataract development was clarified in SRA01/04 cells by overexpression and knockdown of ASAN and further confirmed in cataract rat model. Chromatin immunoprecipitation assay (ChIP) was used to validate the interaction of ATF3 with ASNS.
Induced cataract can be observed in rat eyes at week 2 after exposure to naphthalene. Microarray analysis, realtime-PCR and western blot results showed that the expression of ASNS was upregulated within the first two weeks in rat lens with Naphthalene treatment and then reduced in the later phase. Overexpression of ASNS was able to alleviate cell death, inhibit the oxidation of 1,2-dyhydroxynaphthalene to 1,2-naphthoquinone as well as mitigate the development of naphthalene induced cataract, which suggests that upregulation of ASNS in cataract development involves a protective mechanism. Moreover, ATF3 was confirmed to bind to ASNS promoter and inhibit the expression of ASNS, which indicates that ATF3 inhibiting ASNS expression is a critical etiology of cataract formation.
This study showed that ATF3-ASNS regulation is involved in the naphthalene cataract development. The inhibition of ASNS is the critical etiology of cataract formation. ASNS may be a new target for developing anti-cataract drugs by activation of ASNS.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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