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Abstract #8506 Published in IGR 5-1
Beraprost sodium, a prostaglandin I2 analogue, protects against advanced gycation end products-induced injury in cultured retinal pericytes
Yamagishi S; Amano S; Inagaki Y; Okamoto T; Takeuchi M; Makita ZMolecular Medicine 2002; 8: 546-550
BACKGROUND: Beraprost sodium, a prostaglandin I2 analogue, has been recently reported to exhibit beneficial effects on atherosclerosis in patients with diabetes. However, the effects of beraprost sodium on microvascular injury in diabetes remain to be elucidated. The authors have previously shown that advanced glycation end products (AGE), senescent macroproteins formed at an accelerated rate in diabetes, cause pericyte apoptosis, thus being involved in the pathogenesis of the early phase of diabetic retinopathy. In this study, they examined whether beraprost sodium can protect against AGE-induced cytotoxicity in cultured retinal pericytes. MATERIALS AND METHODS: Intracellular formation of reactive oxygen species (ROS) was detected using a fluorescent probe. DNA synthesis was determined by measuring [3H]thymidine incorporation into cells. Apoptosis was determined by DNA fragmentations, which were quantitatively measured in an enzyme-linked immunosorbent assay. RESULTS: Beraprost sodium or forskolin, a stimulator of adenylate cyclase, was found to significantly inhibit AGE-induced ROS generation and the subsequent decrease in DNA synthesis in pericytes. Both treatments significantly prevented AGE-induced apoptotic cell death in pericytes. Furthermore, beraprost sodium was found to down-regulate AGE receptor mRNA levels in pericytes. CONCLUSION: The results demonstrated that cyclic AMP-elevating agents such as beraprost sodium and forskolin protected retinal pericytes from AGE-induced cytotoxicity through its anti-oxidative properties. The present study suggests that beraprost sodium may have therapeutic potentials in treatment of patients with early diabetic retinopathy.
Dr. S. Yamagishi, Division of Endocrinology and Matabolism, Department of Medicine, Kurume University School of Medicine, Japan. shoichi@med.kurume-u.ac.jp
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
