Luo Lu1, Ling Wang, Beth Shell. 1. Division of Molecular Medicine, Harbor-UCLA Medical Center, UCLA School of Medicine, University of California-Los Angeles, 1124 W. Carson Street, Torrance, CA 90502, USA. lluou@ucla.edu
Abstract
PURPOSE: UV-C irradiation of corneal epithelial cells elicits K+ channel activation, which in turn causes them to undergo apoptosis. In the present study, the intermediary role played by mitogen-activated protein kinase (MAPK) signaling pathways in mediating this response was investigated. METHODS: Western blot and kinase assays were used to measure UV-induced activation (i.e., phosphorylation) of c-Jun NH(2)-terminal kinase (JNK)/SEK, extracellular signal-regulated kinase (ERK), and p38. Corneal epithelial apoptosis was determined by measuring caspase 3 activity. RESULTS: UV-irradiation-induced increases in cell membrane K+ channel activity resulted in activations of JNK, SEK upstream of JNK, and caspase 3 downstream of JNK. Suppression of K+ channel activity with specific K+ channel blockers significantly inhibited UV-irradiation-induced activation of JNK cascades. However, suppression of K+ channel activity did not prevent hyperosmotic-stress-induced JNK activation. In addition, UV-irradiation-induced SEK/JNK activation was unaffected by removal of extracellular free Ca2+ with EGTA. CONCLUSIONS: UV-irradiation-induced corneal epithelial cell apoptosis is mediated through activation of the SEK/JNK signaling pathway. Such activation is dependent on increases in K+ channel activity, which play an important role in the early events that result in activation of this pathway.
PURPOSE: UV-C irradiation of corneal epithelial cells elicits K+ channel activation, which in turn causes them to undergo apoptosis. In the present study, the intermediary role played by mitogen-activated protein kinase (MAPK) signaling pathways in mediating this response was investigated. METHODS: Western blot and kinase assays were used to measure UV-induced activation (i.e., phosphorylation) of c-Jun NH(2)-terminal kinase (JNK)/SEK, extracellular signal-regulated kinase (ERK), and p38. Corneal epithelial apoptosis was determined by measuring caspase 3 activity. RESULTS: UV-irradiation-induced increases in cell membrane K+ channel activity resulted in activations of JNK, SEK upstream of JNK, and caspase 3 downstream of JNK. Suppression of K+ channel activity with specific K+ channel blockers significantly inhibited UV-irradiation-induced activation of JNK cascades. However, suppression of K+ channel activity did not prevent hyperosmotic-stress-induced JNK activation. In addition, UV-irradiation-induced SEK/JNK activation was unaffected by removal of extracellular free Ca2+ with EGTA. CONCLUSIONS: UV-irradiation-induced corneal epithelial cell apoptosis is mediated through activation of the SEK/JNK signaling pathway. Such activation is dependent on increases in K+ channel activity, which play an important role in the early events that result in activation of this pathway.
Authors: Louis Tong; Rosa M Corrales; Zhuo Chen; Arturo L Villarreal; Cintia S De Paiva; Roger Beuerman; De-Quan Li; Stephen C Pflugfelder Journal: Invest Ophthalmol Vis Sci Date: 2006-05 Impact factor: 4.799
Authors: John L Ubels; Rachel E Van Dyken; Julienne R Louters; Mark P Schotanus; Loren D Haarsma Journal: Exp Eye Res Date: 2011-03-04 Impact factor: 3.467