Department of Biology, Calvin College, 3201 Burton St. SE, Grand Rapids, MI 49546, USA.
Exp Eye Res. 2011 Nov;93(5):735-40. doi: 10.1016/j.exer.2011.09.005. Epub 2011 Oct 14.
The goal of this study was to determine whether elevated [K(+)] protects stratified corneal epithelial cells from entering apoptosis following exposure to ambient levels of UVB radiation. Human corneal limbal epithelial (HCLE) cells were stratified to form multilayered constructs in culture. The cells were exposed to UVB doses of 100-250 mJ/cm(2) followed by incubation in medium with 5.5-100 mM K(+). The protective effect of K(+) was determined by measuring the caspase-3 and -8 activity and TUNEL staining of the stratified HCLE constructs. In response to UVB exposure, activation of apoptotic pathways peaked at 24 h. Caspase-8 in stratified cells was activated by exposure to UVB at 100-250 mJ/cm(2), and activity was significantly reduced in response to 50 or 100 mM K(+). Caspase-3 was activated in the stratified cells in response to 100-250 mJ/cm(2) UVB and showed a significant reduction in activity in response to 25, 50 or 100 mM K(+). DNA fragmentation, as indicated by TUNEL staining, was elevated after exposure to 200 mJ/cm(2) UVB, and decreased following incubation with 25-100 mM K(+). These results show that in a culture system that models the intact corneal epithelium, elevated extracellular K(+) can reduce UVB-induced apoptosis which is believed to be initiated by loss of K(+) from cells. This is the basis of damage to the corneal epithelium caused by UVB exposure. Based on these observations it is suggested that the relatively high K(+) concentration in tears (20-25 mM) may play a role in protecting the corneal epithelium from ambient UVB radiation.
本研究旨在确定细胞外[K(+)]升高是否能保护角膜上皮细胞在暴露于环境水平的 UVB 辐射后免于凋亡。我们将人眼角膜缘上皮(HCLE)细胞进行分层培养以形成多层结构。然后用 100-250 mJ/cm(2) 的 UVB 剂量处理细胞,并在含有 5.5-100 mM K(+)的培养基中孵育,以检测 K(+)的保护作用。通过测量分层 HCLE 构建体中的 caspase-3 和 -8 活性和 TUNEL 染色来确定 K(+)的保护作用。对 UVB 暴露的反应,凋亡途径的激活在 24 小时达到峰值。Caspase-8 在分层细胞中被 100-250 mJ/cm(2) 的 UVB 激活,并且对 50 或 100 mM K(+)的反应活性显著降低。Caspase-3 在分层细胞中对 100-250 mJ/cm(2) 的 UVB 作出反应,并对 25、50 或 100 mM K(+)的反应显示活性显著降低。DNA 片段化,如 TUNEL 染色所示,在暴露于 200 mJ/cm(2) 的 UVB 后增加,并在孵育 25-100 mM K(+)后减少。这些结果表明,在一种模拟完整角膜上皮的培养系统中,细胞外[K(+)]升高可以减少 UVB 诱导的凋亡,这种凋亡被认为是由细胞内[K(+)]的丢失引起的。这是 UVB 暴露引起角膜上皮损伤的基础。基于这些观察结果,建议泪液中相对较高的[K(+)]浓度(20-25 mM)可能在保护角膜上皮免受环境 UVB 辐射方面发挥作用。