Purchase this article with an account.
Ling Wang, Luo Lu; Pathway-Specific Effect of Caffeine on Protection against UV Irradiation–Induced Apoptosis in Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(2):652-660. doi: 10.1167/iovs.06-1007.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. To define the role of molecular interaction between the UV-induced JNK (c-Jun N-terminal kinase) cascade and corneal epithelial cell apoptosis and protection against apoptosis by caffeine.
methods. Rabbit and human corneal epithelial cells were cultured in DMEM/F12 medium containing 10% FBS and 5 μg/mL insulin at 37°C in 5% CO2. DNA fragmentation and ethidium bromide/acridine orange (EB/AO) nuclear staining were performed to detect cell death. Western blot, immunoprecipitation, and kinase assays were used to measure UV-induced mitogen-activated protein (MAP) kinase activity.
results. UV irradiation–induced apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and MAKK4 (SEK1) upstream from JNK was caffeine sensitive. Caffeine (1,3,7-trimethylxanthine), an agent that is one of the most popular additions to food consumed in the world and a potential enhancer of chemotherapy, effectively protected corneal epithelial cells against apoptosis by its specific effect on the JNK cascade. Theophylline (1,3-dimethylxanthine) exhibited an effect similar to that of caffeine on prevention of UV irradiation–induced apoptosis. However, alterations of either intracellular cAMP or Ca2+ levels did not alter the effect of caffeine on the JNK signaling pathway. In addition, the blockade of PI3K-like kinases by wortmannin had no impact on the protective effect of caffeine against UV irradiation–induced apoptosis, suggesting that the protective effect of caffeine acts through a specific mechanism involving UV irradiation–induced activation of ASK1 and SEK1. In contrast, caffeine had no effects on melphalan-, hyperosmotic stress–, or IL-1β-induced activation of the JNK signaling pathway in these cells.
conclusions. UV irradiation stress–induced activation of the ASK1-SEK1-JNK signaling pathway leading to apoptosis is a caffeine-sensitive process, and caffeine, as a multifunctional agent in cells, can specifically interact with the pathway to protect against apoptosis.
This PDF is available to Subscribers Only