Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor in bovine retinal pericytes.
The influence of advanced glycation end products (AGEs) on apoptotic cell death and vascular endothelial growth factor (VEGF) gene expression in cultured bovine retinal pericytes was investigated. When pericytes were incubated with three immunochemically distinct AGEs, which were prepared in vitro by incubating bovine serum albumin with glucose, glyceraldehyde, or glycolaldehyde, apoptotic cell death and DNA ladder formation were significantly induced. The cytopathic effects of glyceraldehyde- or glycolaldehyde-derived AGEs were significantly enhanced in AGE receptor-transfected pericytes. Furthermore, all of these AGEs were found to upregulate the secretory forms of VEGF mRNA levels in retinal pericytes. These results suggest that AGEs disturbed retinal microvascular homeostasis by inducing pericyte apoptosis and VEGF overproduction and thus were involved in the pathogenesis of early phase diabetic retinopathy.
Yamagishi
Sho-ichi
S
Division of Endocrinology and Metabolism, Kurume University School of Medicine, Kurume, 830-0011, Japan. shoichi@med.kurume-u.ac.jp
Amano
Shinjiro
S
Inagaki
Yosuke
Y
Okamoto
Tamami
T
Koga
Kohachiro
K
Sasaki
Nobuyuki
N
Yamamoto
Hiroshi
H
Takeuchi
Masayoshi
M
Makita
Zenji
Z
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D005985:Glyceraldehyde / Q000737:chemistry; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D020286:Pericytes / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000096:biosynthesis; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D017127:Glycation End Products, Advanced; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012710:Serum Albumin, Bovine; D005985:Glyceraldehyde; D004247:DNA; D000079:Acetaldehyde; C010972:glycolaldehyde