title: Elevated Nε-(carboxymethyl)lysine is associated with apoptosis of retinal pericytes in streptozotocin-induced diabetic rats.
abstract: Advanced glycation end products including Nε-(carboxymethyl)lysine (CML) are believed to contribute to retinal pericyte loss in diabetic retinopathy. Nuclear factor-κB (NF-κB) activation has been considered as a potential cytotoxic modulator of retinal pericytes. Herein, we investigated whether CML accumulation can trigger NF-κB activation and apoptosis of retinal pericytes in streptozotocin (STZ)-induced diabetic rats. Seven-week-old Sprague-Dawley rats were made diabetic (STZ, 60 mg/kg). After 5 months, CML level and NF-κB activation were measured in trypsin-digested retinal vessels. In diabetic rats, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive and caspase 3-positive retinal pericytes were significantly increased. CML and NF-κB activation was also markedly increased in diabetic retinal vessels. Moreover, the immunoreactivity of NF-κB was localized within the region where CML were accumulated. Apoptosis occurred in CML-accumulating retinal pericytes. These results suggest that NF-κB could be activated in CML-accumulating pericytes from diabetic retina. CML accumulation is responsible, at least in part, for the apoptosis of retinal pericytes.
authors.affiliation: Diabetic Complications Research Center, Division of Traditional Korean Medicine Integrated Research Korea Institute of Oriental Medicine, Daejeon, South Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Kim
authors.forename: Eunjin
authors.initials: E
authors.lastname: Sohn
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D017127:Glycation End Products, Advanced / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology*
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; C048496:N(6)-carboxymethyllysine; D053148:Caspase 3; D008239:Lysine