Light-induced resistance of the keratin network to the filament-disrupting tyrosine phosphatase inhibitor orthovanadate.
Epidermal keratinocytes respond to low-dose light irradiation by inducing signaling cascades that lead to long-term effects on gene transcription thereby protecting cells against damage. In contrast, little is known about immediate light-induced alterations of structural proteins. We have made the intriguing observation that light produces fundamental changes in the properties of the keratin filament system of cultured epidermoid A-431 cells. A short light exposure (1-10 min) causes the keratin cytoskeleton to become immediately resistant to the tyrosine phosphatase inhibitor orthovanadate, which otherwise disrupts the keratin filament network completely in just a few minutes. This protective effect is inducible throughout the entire visible spectrum and is elicited by normal room light (<200 Lux). Exposure of cells to monochromatic light of various wavelengths is therefore equally effective. In addition, the acquisition of orthovanadate resistance has been directly monitored in living cells; a partially disrupted keratin cytoskeleton recovers to a completely filamentous network in half an hour. Finally, the protective light effect is largely reversed in 2 h and can be mimicked by preincubation with the p38 kinase inhibitor SB203580. In contrast, the mitogen-activated protein kinase inhibitor PD98059 and epidermal growth factor inhibit orthovanadate action to a lesser extent. Taken together, these observations suggest a stabilizing function of light on the keratin filament network; this may be of relevance to the treatment of skin diseases with reduced keratin stability.
Strnad
Pavel
P
Department of Anatomy, Johannes Gutenberg-University, Mainz, Germany.
Windoffer
Reinhard
R
Leube
Rudolf E
RE
D004351:Drug Resistance / Q000528:radiation effects; D000078404:Epidermal Cells; D005260:Female; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects* / Q000528:radiation effects; D007633:Keratins / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014638:Vanadates / Q000494:pharmacology*; D014846:Vulvar Neoplasms
D014638:Vanadates; D007633:Keratins; D017027:Protein Tyrosine Phosphatases