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Bingqian Liu, Jian Ge; Transient Upregulation and then Downregulation of BACE 1 and PS-1 in ER Stress Induced Apoptosis of Retinal Ganglion Cells in vitro. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6114.
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To investigate the level of beta-secretase 1 (BACE-1), presenilin-1 (PS-1) and full length amyloid precursor protein (APP) in Endoplasmic Reticulum (ER) stress induced retinal ganglion cell apoptosis in vitro.
Tunicamycin (Tm, 2μg/ml) were added for 48 hours to induce ER stress in retinal ganglion cells (RGC-5 cell line) cultured in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum. Protein levels of 78 kDa glucose-regulated protein (GRP-78), full length APP, BACE1, PS-1, and cleaved caspase 3 were examined by western blot analysis.
ER stress marker GRP-78 was increased in RGC-5 cells treated with Tm in a time-dependent manner. Protein level of full length APP was decreased steadily after Tm treatment. BACE-1, and PS-1 were both increased significantly at 2 hour time point in Tm group compared to vehicle control. Then, BACE-1 decreased rapidly, while PS-1 decreased slowly, to an undetectable level. Cleaved caspase-3 was increased significantly under ER stress.
BACE-1 and PS-1 were initially increased and then decreased in ER stress induced apoptosis of retinal ganglion cells in vitro. Full length APP might be cleaved by the transient upregulation of BACE-1 and PS-1. Further study is needed to determine whether there is a negative feedback between the production of amyloid beta and the BACE-1 and PS-1 activities in this process.
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