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| ADVANCED GLYCATION END-PRODUCTS INDUCE APOPTOSIS AND THE SIGNALING PATHWAY IN BOVINE RETINAL PERICYTES |
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| 作者：Chen Bai… 文章来源：Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha,410011 点击数1147 更新时间：2005/6/13 22:19:07 文章录入：cbhzndxcbh 责任编辑：毛进 |
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| Background: One of the histopathologic hallmarks of early diabetic retinopathy is the selective loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. We tested the hypothesis that advanced glycation end products might be involved in the disappearance of retinal pericytes by apoptosis and further investigated the signaling pathway leading to cell death.
Methods: Cultured bovine retinal microvascular pericytes were exposed to various concentrations of advanced glycation end products-bovine serum albumin (0.47, 1.88, 7.5, 30 μM) for 4 days. We assayed the degree of pericytes apoptosis by FACS (fluorescence activated cell sorting), and further measured intracellular catalase and superoxide dismutase (SOD) activities; malondialdehyde productions; Bcl-2/Bax ratio; and caspase-3 activity.
Results: After a 4-day incubation, advanced glycation end products-bovine serum albumin could induce significantly the apoptosis of bovine retinal microvascular pericytes in a dose-dependent manner compared with controls, associated with an increase in intracellular malondialdehyde level and caspase-3 activity; a decrease in intracellular catalase, SOD activities and Bcl-2/Bax ratio. SOD and selective caspase-3 inhibitor Z-DEVD-fmk can inhibit pericyte apoptosis induced by AGE-BSA.
Conclusion: These results suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that elevated advanced glycation end products observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism. The decreased Bcl-2/Bax ratio and activation of caspase-3 are associated with apoptotic process.
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