Oxidant-induced apoptosis in human retinal pigment epithelial cells: Dependence on extracellular redox state
Oxidant-induced apoptosis in human retinal pigment epithelial cells: Dependence on extracellular redox state
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DOI：
10.1167/iovs.04-0949
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Jones, DP
中科院分区：
文献类型：
--
作者：
Jiang, SN;Moriarty-Craige, SE;Jones, DP
目的。检测人血浆中细胞外半胱氨酸（Cys）氧化还原电位（E-h）在生理范围内的变化是否影响氧化诱导的培养人视网膜色素上皮（hRPE）细胞凋亡。hRPE细胞在- 16 mV（最氧化）至- 158 mV（最还原）范围内的培养基中培养，加入不同浓度的Cys和胱氨酸（CySS），总Cys当量恒定。过氧化叔丁基（tBH）诱导细胞凋亡。与还原条件（E-h < -89 mV）相比，高氧化条件（E-h > - 55 mV）下hRPE细胞对tbh诱导的凋亡更敏感。在氧化程度更高的条件下，tBH处理后线粒体膜电位损失（δ psi(m)）、细胞色素c的释放和caspase 3的激活均增加。然而，在hRPE细胞中，细胞外氧化还原状态不影响Fas或Fast的表达。暴露于更氧化的细胞外氧化还原环境的hRPE细胞通过固有的线粒体途径增加了氧化诱导的细胞凋亡的易感性，这可能导致视网膜细胞群的年龄相关下降，从而为与年龄相关的黄斑变性（ARMD）相关的退行性变化提供了潜在的机制。
PURPOSE. To test whether variation in extracellular cysteine (Cys) redox potential (E-h) over the physiologic range occurring in human plasma affects oxidant-induced apoptosis in cultured human retinal pigment epithelial (hRPE) cells.METHODS. The hRPE cells were incubated in culture medium with E-h established over the range of - 16 mV (most oxidized) to - 158 mV (most reduced) by adding different concentrations of Cys and cystine (CySS) with constant total Cys equivalents. Apoptosis was induced with tert-butylhydroperoxide (tBH).RESULTS. The hRPE cells were sensitized to tBH-induced apoptosis in the more oxidized extracellular conditions (E-h > - 55 mV) compared with the reduced conditions (E-h < -89 mV). Loss of mitochondrial membrane potential (Delta psi(m)), release of cytochrome c, and activation of caspase 3 after tBH treatments all increased under the more oxidized conditions. However, the extracellular redox state did not affect expression of Fas or Fast, in hRPE cells.CONCLUSIONS. The hRPE cells that are exposed to a more oxidized extracellular redox environment have increased susceptibility to oxidant-induced apoptosis through the intrinsic mitochondrial pathway, which could contribute to an age-related decline in cell populations in the retina and thereby provide a potential mechanism for the degenerative changes that are associated with age-related macular degeneration (ARMD).