TNF-R1 and FADD mediate UVB-Induced activation of K + channels in corneal epithelial cells.

Autor: Boersma PM; Department of Biology, Calvin College, 3201 Burton St. SE, Grand Rapids, MI 49546, USA; Department of Physics and Astronomy, Calvin College, 3201 Burton St. SE, Grand Rapids, MI 49546, USA., Haarsma LD; Department of Physics and Astronomy, Calvin College, 3201 Burton St. SE, Grand Rapids, MI 49546, USA., Schotanus MP; Department of Biology, Calvin College, 3201 Burton St. SE, Grand Rapids, MI 49546, USA., Ubels JL; Department of Biology, Calvin College, 3201 Burton St. SE, Grand Rapids, MI 49546, USA. Electronic address: jubels@calvin.edu.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2017 Jan; Vol. 154, pp. 1-9. Date of Electronic Publication: 2016 Nov 03.
DOI: 10.1016/j.exer.2016.11.003
Abstrakt: The goal of this study was to elucidate the role of Fas, TNF-R1, FADD and cytochrome c in UVB-induced K + channel activation, an early step in UVB-induced apoptosis, in human corneal limbal epithelial (HCLE) cells. HCLE cells were treated with Fas, TNF-R1 or FADD siRNA and exposed to 80 or 150 mJ/cm 2 UVB. K + channel activation and loss of intracellular K + were measured using whole-cell patch-clamp recording and ion chromatography, respectively. Cytochrome c was measured with an ELISA kit. Cells in which Fas was knocked down exhibited identical UVB-induced K + channel activation and loss of intracellular K + to control cells. Cells in which TNF-R1 or FADD were knocked down demonstrated reduced K + channel activation and decreased loss of intracellular K + following UVB, relative to control cells. Application of TNF-α, the natural ligand of TNF-R1, to HCLE cells induced K + channel activation and loss of intracellular K + . Cytochrome c was translocated to the cytosol by 2 h after exposure to 150 mJ/cm 2 UVB. However, there was no release by 10 min post-UVB. The data suggest that UVB activates TNF-R1, which in turn may activate K + channels via FADD. This conclusion is supported by the observation that TNF-α also causes loss of intracellular K + . This signaling pathway appears to be integral to UVB-induced K + efflux, since knockdown of TNF-R1 or FADD inhibits the UVB-induced K + efflux. The lack of rapid cytochrome c translocation indicates cytochrome c does not play a role in UVB-induced K + channel activation.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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