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.
Keywords:
Fas–FasL; advanced glycation end-product (AGE); apoptosis; human retinal cells; mitochondrial dysfunction.
MeSH terms
-
Apoptosis / drug effects*
-
Caspase 3 / genetics
-
Caspase 3 / metabolism
-
Caspase 8 / genetics
-
Caspase 8 / metabolism
-
Cell Line
-
Epithelial Cells / drug effects*
-
Epithelial Cells / metabolism
-
Fas Ligand Protein / agonists
-
Fas Ligand Protein / antagonists & inhibitors
-
Fas Ligand Protein / genetics*
-
Fas Ligand Protein / metabolism
-
Gene Expression Regulation
-
Glycation End Products, Advanced / pharmacology*
-
Humans
-
Membrane Potential, Mitochondrial / drug effects
-
Mitochondria / drug effects*
-
Mitochondria / metabolism
-
Proto-Oncogene Proteins c-bcl-2 / genetics
-
Proto-Oncogene Proteins c-bcl-2 / metabolism
-
RNA, Small Interfering / genetics
-
RNA, Small Interfering / metabolism
-
Recombinant Fusion Proteins / pharmacology
-
Retina / drug effects
-
Retina / metabolism
-
Serum Albumin, Bovine / pharmacology
-
Signal Transduction
-
fas Receptor / agonists
-
fas Receptor / antagonists & inhibitors
-
fas Receptor / genetics*
-
fas Receptor / metabolism
Substances
-
BCL2 protein, human
-
FAS protein, human
-
FASLG protein, human
-
Fas Ligand Protein
-
Glycation End Products, Advanced
-
Proto-Oncogene Proteins c-bcl-2
-
RNA, Small Interfering
-
Recombinant Fusion Proteins
-
fas Receptor
-
Serum Albumin, Bovine
-
Casp3 protein, mouse
-
Casp8 protein, mouse
-
Caspase 3
-
Caspase 8