UV-induced signaling pathways associated with corneal epithelial cell apoptosis.
OBJECTIVE
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.
Lu
Luo
L
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
Wang
Ling
L
Shell
Beth
B
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D019573:Epithelium, Corneal / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011817:Rabbits; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D004533:Egtazic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D011188:Potassium; D002118:Calcium