title: Advanced glycation end-product (AGE) induces apoptosis in human retinal ARPE-19 cells via promoting mitochondrial dysfunction and activating the Fas-FasL signaling.
abstract: Advanced glycation end-products (AGEs) are extremely accumulated in the retinal vascular and epithelial cells of diabetes mellitus (DM) patients, particularly with diabetic retinopathy (DR). To elucidate the pathogenesis of the AGE-induced toxicity to retinal epithelial cells, we investigated the role of Fas-Fas ligand (FasL) signaling and mitochondrial dysfunction in the AGE-induced apoptosis. Results demonstrated that the AGE-BSA- induced apoptosis of retinal ARPE-19 cells. And the AGE-BSA treatment caused mitochondrial dysfunction, via deregulating the B-cell lymphoma 2 (Bcl-2) signaling. Moreover, the Fas/FasL and its downstreamer Caspase 8 were promoted by the AGE-BSA treatment, and the exogenous α-Fas exacerbated the activation of Caspase 3/8. On the other side, the siRNA-mediated knockdown of Fas/FasL inhibited the AGE-BSA-induced apoptosis. Taken together, we confirmed the activation of Fas-FasL signaling and of mitochondrial dysfunction in the AGE-BSA-promoted apoptosis in retinal ARPE-19 cells, implying the important role of Fas-FasL signaling in the DR in DM.
authors.affiliation: a Department of Ophthalmology , Renmin Hospital of Wuhan University , Wuhan , People's Republic of China.|b Department of Ophthalmology , Inner Mongolia People's Hospital , Hohhot , People's Republic of China.
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.affiliation: a Department of Ophthalmology , Renmin Hospital of Wuhan University , Wuhan , People's Republic of China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Xing
authors.affiliation: a Department of Ophthalmology , Renmin Hospital of Wuhan University , Wuhan , People's Republic of China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: a Department of Ophthalmology , Renmin Hospital of Wuhan University , Wuhan , People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: b Department of Ophthalmology , Inner Mongolia People's Hospital , Hohhot , People's Republic of China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Qian
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction; D019014:fas Receptor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017127:Glycation End Products, Advanced; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D012710:Serum Albumin, Bovine; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8
keywords: Fas–FasL; advanced glycation end-product (AGE); apoptosis; human retinal cells; mitochondrial dysfunction