title: Glucocorticoid receptors take part in the apoptotic process of human lens epithelial cells, but the glucocorticoid receptor antagonist RU486 does not rescue the cells fully.
abstract: To identify an agent with specific activity against human lens epithelial cells (HLECs), we confirmed the presence of glucocorticoid receptors (GRs) and GR-α genes and evaluated whether GRs have a relationship with the apoptotic process in cultured HLECs. We also determined whether the inhibitor RU486 could rescue the cells from apoptosis when the HLECs were exposed to dexamethasone (Dex), a steroid, in 4 concentrations for 4 periods, or were co-treated with the antagonist RU486. We found that Dex, which has been used as a medical agent for a long time, resulted in increased expression of GRE-luciferase, the GR-α gene and GR-protein and, in contrast, decreased the viability of HLECs. The expression of Bax protein was increased in an earlier stage in contrast to the expression of Bcl-2 protein, which was increased in a later stage. Caspase-3 activity was significantly increased under lower concentrations of Dex in the last stage. The nuclear morphology of HLECs showed an obvious apoptotic phenomenon under greater concentrations of Dex in the last stage. However, RU486, a GR antagonist, could partially inhibit GR and Bax expressions and the expression of caspase-3 was increased so that there was not a decrease in the ratio of apoptotic cells and an increase in the viability of HLECs. Our data showed that GRs had a partial relationship to the apoptotic process of HLECs when exposed to Dex and RU486 did not rescue the cells fully. Because of its toxicity, RU486 did not provide a therapeutic benefit in a glucocorticoid induced cataract (GIC) for the in vitro model, however, its activity and pathway targeting should still be studied further with appropriate drug combinations.
authors: Eye Hospital, First Affiliated Hospital, Harbin Medical University, 23 Youzheng Road, Harbin 150001, China.
authors: Lin
authors: L
authors: Wang
authors: Wencheng
authors: W
authors: Zhao
authors: Fei
authors: F
authors: Leng
authors: Jinying
authors: J
authors: Ge
authors: Zhigao
authors: Z
authors: Bu
authors: Yi
authors: Y
authors: Zhang
authors: Ping
authors: P
authors: Liu
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D053144:Cell Nucleus Shape / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002875:Chromosomes / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D057075:Enzyme Assays; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015870:Gene Expression; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D015735:Mifepristone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D049410:Luciferases, Renilla; C505407:CASP3 protein, human; D053148:Caspase 3