Retinal pigment epithelium rescues vascular endothelium from retinoic acid-induced apoptosis.
Retinal pigment epithelium rescues vascular endothelium from retinoic acid-induced apoptosis.
复制标题
视网膜色素上皮将血管内皮从视黄酸诱导的细胞凋亡中拯救出来。
DOI：
10.1167/iovs.05-1557
复制
发表时间：
2006
影响因子：
4.4
通讯作者：
DelPriore,LucianV
中科院分区：
文献类型：
--
作者：
Tezel,TongalpH;Geng,Lijun;Kaplan,HenryJ;DelPriore,LucianV
目的。确定类维甲酸是否能够诱导血管内皮细胞凋亡，以及完整的RPE单层是否可以阻止类维甲酸诱导的血管内皮细胞死亡。融合胎牛主动脉内皮（FBAE）细胞与不同浓度的全反式或9顺式维甲酸（11顺式维甲酸的类似物）孵育。以0.1 mg/mL环己亚胺和10 nM肉豆酸酯佛波酯为培养基，观察24 h细胞凋亡率，并观察抑制蛋白合成和激活蛋白激酶C对细胞凋亡的影响。为了研究RPE对类维甲酸诱导的细胞凋亡的影响，在插入物中加入RPE融合层培养FBAE细胞，在插入物中加入类维甲酸。以牛角膜内皮单层为对照。测定了RPE和牛角膜内皮单层对荧光素（20 μg/mL）和9-顺式维甲酸（3× 10−4 M）的通透性。9-顺式维甲酸诱导FBAE细胞凋亡率高于全反式维甲酸和对照组（P= 0.004）。该效应呈剂量依赖性，ED 50为1.4 μM （r= 0.99， P= 0.004）。环己亚胺对9-顺式维甲酸诱导的细胞凋亡无抑制作用，但肉豆蔻酸酯能显著降低细胞凋亡率（P= 0.005）。融合RPE单层的存在降低了9-顺式维甲酸诱导的细胞凋亡率（P= 0.002），但牛角膜内皮单层的存在没有降低细胞凋亡率（P= 0.05）。两种细胞类型对荧光素和9-顺式维甲酸建立了相似的扩散屏障。9-顺式维甲酸是血管内皮细胞凋亡的重要介质。融合的RPE单层可以防止内皮细胞凋亡，这种作用不仅仅是由于RPE建立了扩散屏障。
purpose. To determine whether retinoids are capable of inducing vascular endothelial cell apoptosis and whether the presence of an intact RPE monolayer can block retinoid-induced vascular endothelial cell death.methods. Confluent fetal bovine aortic endothelial (FBAE) cells were incubated with various concentrations of all-trans or 9-cis retinoic acid (an analogue of 11-cis retinoic acid). Apoptosis rates were determined at 24 hours, and the effect of inhibition of protein synthesis and activation of protein kinase C on apoptosis was investigated by supplying culture medium with 0.1 mg/mL cycloheximide and 10 nM phorbol myristate acetate. To investigate the impact of RPE on retinoid-induced apoptosis, confluent FBAE cells were cultured with a confluent layer of RPE in inserts where retinoids were added to the upper compartment. A confluent bovine corneal endothelium monolayer was used as the control. The permeabilities of the RPE and bovine corneal endothelium monolayers to fluorescein (20 μg/mL) and 9-cis retinoic acid (3× 10− 4 M) were also determined.results. 9-cis Retinoic acid induced higher rates of apoptosis in FBAE cells than did all-trans retinoic acid and the control (P= 0.004). This effect was dose-dependent, with an ED 50 of 1.4 μM (r= 0.99, P= 0.004). Cycloheximide did not inhibit 9-cis retinoic acid–induced apoptosis, but phorbol myristate acetate significantly decreased the apoptosis rate (P= 0.005). The presence of a confluent RPE monolayer reduced the 9-cis retinoic acid–induced apoptosis rate (P= 0.002), but the presence of a bovine corneal endothelial monolayer did not (P> 0.05). Both cell types established a similar diffusion barrier against fluorescein and 9-cis retinoic acid.conclusions. 9-cis Retinoic acid is an important mediator of vascular endothelial apoptosis. A confluent monolayer of RPE can prevent endothelial cell apoptosis, and this effect is not due simply to establishment of a diffusion barrier by the RPE.