title: AGEs Promote Oxidative Stress and Induce Apoptosis in Retinal Pigmented Epithelium Cells RAGE-dependently.
abstract: Advanced glycation end products (AGEs) are extremely accumulated in diabetes mellitus, particularly in retinal vascular and epithelium cells, and are confirmed to contribute to diabetic retinopathy (DR). In the present study, we determined the promotion by AGEs to the oxidative stress and mitochondrial dysfunction in retinal pigmented epithelium ARPE-19 cells and investigated the influence by the knockdown or the overexpression of receptor for AGEs (RAGE) on the AGE-promoted oxidative stress and mitochondrial dysfunction. Furthermore, we determined the induction by AGEs to the cell apoptosis and to the activation of B-cell lymphoma 2 (Bcl-2) families in the AGE-BSA-induced apoptosis, and examined the RAGE-dependence in such induction. Results demonstrated that AGE-BSA upregulated the hydrogen peroxide production and induced mitochondrial dysfunction in ARPE-19 cells, dose-dependently. And the further investigation indicated that the AGE-RAGE interaction was required for the induction of oxidative stress and mitochondrial dysfunction. Moreover, the AGE-BSA treatment promoted a significantly high level of apoptotic cells, and the Bcl-2 family was implicated in the AGE-BSA-induced apoptosis, there was a significant high level of Cyt c release, Bcl-2-associated X protein (Bax) induction, Bcl-2 reduction, and caspase 9 activation in the AGE-BSA-treated cells. In conclusion, the present study recognized the apoptosis induction by AGE-BSAs in the retinal epithelium ARPE-19 cells, RAGE-dependently. The mitochondrial dysfunction was induced, and the Bcl-2 family was deregulated during the AGE-BSA-induced ARPE-19 cell apoptosis.
authors: Department of Ophthalmology, The Fourth Affiliated Hospital, China Medical University, No. 11 Xinhua Road, Heping District, Shenyang, 110005, China, xinling1023wang@163.com.
authors: Xin-Ling
authors: XL
authors: Wang
authors: Tao
authors: T
authors: Yu
authors: Qi-Chang
authors: QC
authors: Yan
authors: Wei
authors: W
authors: Wang
authors: Nan
authors: N
authors: Meng
authors: Xue-Jiao
authors: XJ
authors: Li
authors: Ya-Hong
authors: YH
authors: Luo
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products