Beraprost sodium, a prostaglandin I2 analogue, protects against advanced gycation end products-induced injury in cultured retinal pericytes.
BACKGROUND
Beraprost sodium, a prostaglandin I2 analogue, has been recently reported to exhibit beneficial effects on atherosclerosis in patients with diabetes. However, effects of beraprost sodium on microvascular injury in diabetes remain to be elucidated. We have previously shown that advanced glycation end products (AGE), senescent macroproteins formed at an accelerated rate in diabetes, caused pericyte apoptosis, thus being involved in the pathogenesis of the early phase of diabetic retinopathy. In this study, we examined whether beraprost sodium can protect against AGE-induced cytotoxicity in cultured retinal pericytes.


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.


CONCLUSIONS
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. Our present study suggests that beraprost sodium may have therapeutic potentials in treatment of patients with early diabetic retinopathy.
Yamagishi
Sho-ichi
S
Division of Endocrinology and Matabolism, Department of Medicine, Kurume University School of Medicine, Japan. shoichi@med.kurume-u.ac.jp
Amano
Shinjiro
S
Inagaki
Yosuke
Y
Okamoto
Tamami
T
Takeuchi
Masayoshi
M
Makita
Zenji
Z
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D020286:Pericytes / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D012160:Retina / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014665:Vasodilator Agents; D005576:Colforsin; C048081:beraprost; D004247:DNA; D011464:Epoprostenol